Belinda Rivera-Lebron

Echocardiographic and Hemodynamic Predictors of Mortality in Idiopathic Pulmonary Fibrosis

BACKGROUND Idiopathic pulmonary fibrosis (IPF) can lead to the development of pulmonary hypertension, which is associated with an increased risk of death. In pulmonary arterial hypertension, survival is directly related to the capacity of the right ventricle to adapt to elevated pulmonary vascular load. The relative importance of right ventricular function in IPF is not well understood. Our objective was to evaluate right ventricular echocardiographic and hemodynamic predictors of mortality in a cohort of patients with IPF referred for lung transplant evaluation. METHODS We performed a retrospective cohort study of 135 patients who met 2011 American Thoracic Society/European Respiratory Society criteria for IPF and who were evaluated for lung transplantation at the Hospital of the University of Pennsylvania. RESULTS Right ventricle:left ventricle diameter ratio (hazard ratio [HR], 4.5; 95% CI, 1.7-11.9), moderate to severe right atrial and right ventricular dilation (HR, 2.9; 95% CI, 1.4-5.9; and HR, 2.7; 95% CI, 1.4-5.4, respectively) and right ventricular dysfunction (HR, 5.5; 95% CI, 2.6-11.5) were associated with an increased risk of death. Higher pulmonary vascular resistance was also associated with increased mortality (HR per 1 Wood unit, 1.3; 95% CI, 1.1-1.5). These risk factors were independent of age, sex, race, height, weight, FVC, and lung transplantation status. Other hemodynamic indices, such as mean pulmonary artery pressure and cardiac index, were not associated with outcome. CONCLUSIONS Right-sided heart size and right ventricular dysfunction measured by echocardiography and higher pulmonary vascular resistance by invasive hemodynamic assessment predict mortality in patients with IPF evaluated for lung transplantation.

Exposure to Ambient Particulate Matter Is Associated With Accelerated Functional Decline in Idiopathic Pulmonary Fibrosis

Background Idiopathic pulmonary fibrosis (IPF), a progressive disease with an unknown pathogenesis, may be due in part to an abnormal response to injurious stimuli by alveolar epithelial cells. Air pollution and particulate inhalation of matter evoke a wide variety of pulmonary and systemic inflammatory diseases. We therefore hypothesized that increased average ambient particulate matter (PM) concentrations would be associated with an accelerated rate of decline in FVC in IPF. Methods We identified a cohort of subjects seen at a single university referral center from 2007 to 2013. Average concentrations of particulate matter < 10 and < 2.5 &mgr;g/m3 (PM10 and PM2.5, respectively) were assigned to each patient based on geocoded residential addresses. A linear multivariable mixed‐effects model determined the association between the rate of decline in FVC and average PM concentration, controlling for baseline FVC at first measurement and other covariates. Results One hundred thirty‐five subjects were included in the final analysis after exclusion of subjects missing repeated spirometry measurements and those for whom exposure data were not available. There was a significant association between PM10 levels and the rate of decline in FVC during the study period, with each &mgr;g/m3 increase in PM10 corresponding with an additional 46 cc/y decline in FVC (P = .008). Conclusions Ambient air pollution, as measured by average PM10 concentration, is associated with an increase in the rate of decline of FVC in IPF, suggesting a potential mechanistic role for air pollution in the progression of disease.

Ultrasound-Assisted Catheter-Directed Thrombolysis: A Novel and Promising Endovascular Therapeutic Modality for Intermediate-Risk Pulmonary Embolism.

Intermediate-risk pulmonary embolism (PE), also known as submassive PE, occurs in a substantial group of patients and carries a significant mortality risk. With adequate risk stratification, catheter-directed techniques could be used as a therapeutic approach in the intermediate-risk PE. Ultrasound-assisted catheter-directed thrombolysis (UCDT) represents a novel endovascular technique with good clinical and safety outcomes. Ultrasound-assisted catheter-directed thrombolysis can achieve reduction in the thrombus burden and improvement of pulmonary hemodynamics and right ventricular (RV) dysfunction and/or dilatation, without major procedure-related complications, major bleeding, or hemorrhagic strokes. This narrative review will focus on the major studies involving the efficacy and safety of UCDT in the intermediate-risk PE population. Prospective, randomized clinical trials with long-term follow-up and a large sample size are needed for further evaluation of mortality benefit and to further define which subgroup of patients may benefit from this novel endovascular technique.

Ambrisentan: a review of its use in pulmonary arterial hypertension:

Pulmonary arterial hypertension (PAH) is a progressive disease defined by an elevation in pulmonary arterial pressure that can lead to right heart failure and death. Ambrisentan is a selective endothelin receptor antagonist approved for the treatment of idiopathic, heritable PAH and connective tissue disease-associated PAH. Ambrisentan has been shown to improve exercise capacity and hemodynamics with an acceptable side-effect profile. It has also proven to be safely used in combination with other PAH-specific medications, especially with phosphodiesterase-5 inhibitors. In the recent randomized trial, AMBITION, it was shown that upfront combination therapy of ambrisentan and tadalafil significantly decreased the risk of clinical failure compared with monotherapy. This review describes the drug profile of ambrisentan and its safety and efficacy in the treatment of PAH.

Impact of four times daily dosing of oral treprostinil on tolerability and daily dose achieved in pulmonary hypertension

Oral treprostinil (TRE) is a prostacylin that is approved for the treatment of patients with pulmonary arterial hypertension (PAH). Dosing is approved for two or three times daily (t.i.d.); however, adverse effects, including gastrointestinal-related symptoms, may limit the ability to reach optimal doses. We report our experience with a four times daily (q.i.d.) regimen of oral TRE for goal-directed therapy of PAH. We describe three patients that were transitioned from infusion or inhaled TRE to oral TRE with initial t.i.d. dosing over a four-day hospital stay. All patients were subsequently further dose-adjusted in the outpatient setting; however, adverse effects limited additional up-titration despite persistent dyspnea. In a carefully monitored outpatient setting, patients were switched from t.i.d. to q.i.d. dosing of oral TRE. All three patients were successfully dosed q.i.d., having achieved a higher total daily dose compared with a t.i.d. dose regimen. Furthermore, patients were able to maintain functional class II symptoms with mitigation of adverse effects using the q.i.d. dose regimen.

TCT-779 Catheter-directed Thrombolysis vs. Systemic Thrombolysis in Acute PE: A Single Center Experience

Catheter-directed thrombolysis (CDT) for acute pulmonary embolism (PE) has emerged as an alternative to systemic thrombolysis (ST) in patients with massive and submassive PE. ST in patients with submassive PE is effective at reducing PE related morbidity compared to heparin alone, however the net

Apixaban or Rivaroxaban Versus Warfarin for Treatment of Submassive Pulmonary Embolism After Catheter-Directed Thrombolysis:

Background: Little data exist on the use of direct oral anticoagulant (DOAC) factor Xa inhibitors for submassive pulmonary embolism (PE) after catheter-directed thrombolysis (CDT). The objective of this evaluation was to determine whether the transition from parenteral anticoagulation to DOACs for submassive PE after CDT would decrease hospital length of stay (LOS) compared to warfarin. Methods: A retrospective review of patients diagnosed with submassive PE who underwent CDT was conducted from January 1, 2012, to February 28, 2017. Hospital LOS and major and minor bleeding events were recorded during hospitalization and at 90 days. Results: Sixty-two patients met the inclusion criteria, 36 in warfarin group and 26 in the DOAC group. Overall, patients receiving rivaroxaban or apixaban had a shorter median hospital LOS compared to warfarin (4.0 vs 6.1 days, P = .002). In the multivariate regression analysis, administration of DOAC was an independent predictor of decreased hospital LOS, β: −2.1, 95% confidence interval (−3.5 to −0.7). Conclusion: Among patients with submassive PE, initiation of a DOAC shortly after CDT may result in a decreased hospital LOS compared to parenterally bridged warfarin.

Thrombophilias and Acute Pulmonary Thromboembolic Disease

Venous thrombosis can be divided into two groups: hereditary and acquired thrombophilias. In this chapter, we first introduce the inherited thrombophilias, including Factor V Leiden mutation, prothrombin gene mutation, and protein S and C deficiency. Then we discuss the acquired thrombophilic states, including paroxysmal nocturnal hemoglobinuria, heparin-induced thrombocytopenia, antiphospholipid syndrome, and myeloproliferative neoplasms. We finalize the discussion with the most common presentation of venous thrombosis: deep venous thrombosis and pulmonary embolism.

Determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis undergoing lung transplant evaluation

Little is known about the physiologic determinants of 6-minute walk distance in idiopathic pulmonary fibrosis. We investigated the demographic, pulmonary function, echocardiographic, and hemodynamic determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis evaluated for lung transplantation. We performed a cross-sectional analysis of 130 patients with idiopathic pulmonary fibrosis who completed a lung transplantation evaluation at the Hospital of the University of Pennsylvania between 2005 and 2010. Multivariable linear regression analysis was used to generate an explanatory model for 6-minute walk distance. After adjustment for age, sex, race, height, and weight, the presence of right ventricular dilation was associated with a decrease of 50.9 m (95% confidence interval [CI], 8.4–93.3) in 6-minute walk distance (P = 0:02). For each 200-mL reduction in forced vital capacity, the walk distance decreased by 15.0 m (95% CI, 9.0–21.1; P < 0:001). For every increase of 1 Wood unit in pulmonary vascular resistance, the walk distance decreased by 17.3 m (95% CI, 5.1–29.5; P = 0:006). Six-minute walk distance in idiopathic pulmonary fibrosis depends in part on circulatory impairment and the degree of restrictive lung disease. Future trials that target right ventricular morphology, pulmonary vascular resistance, and forced vital capacity may potentially improve exercise capacity in patients with idiopathic pulmonary fibrosis.