Anjali Vaidya

Changes in right heart haemodynamics and echocardiographic function in an advanced phenotype of pulmonary hypertension and right heart dysfunction associated with pulmonary fibrosis

Background Pulmonary hypertension (PH)-targeted therapy in the setting of pulmonary fibrosis (PF) is controversial; the main clinical concern is worsening of systemic hypoxaemia. We sought to determine the effects of gentle initiation and chronic administration of parenteral treprostinil on right heart function in patients with PF associated with an advanced PH phenotype. Methods Open-label, prospective analysis of patients with PF-PH referred for lung transplantation (LT). Advanced PH was defined as mean pulmonary artery pressure (mPAP) ≥35u2005mmu2005Hg. We compared haemodynamics, Doppler echocardiography (DE), oxygenation, dyspnoea and quality of life indices, and 6 min walk distance (6MWD) before and 12u2005weeks after parenteral treprostinil. Results 15 patients were recruited in the study. After therapy, there were significant improvements in right heart haemodynamics (right atrial pressure (9.5u2009±u20093.4 vs 6.0u2009±u20093.7); mPAP (47u2009±u20098 vs 38.9u2009±u200913.4); CI (2.3u2009±u20090.5 vs 2.7u2009±u20090.6); pulmonary vascular resistance (698u2009±u2009278 vs 496u2009±u2009229); transpulmonary gradient (34.7u2009±u20098.7 vs 28.5u2009±u200910.3); mvO2 (65u2009±u20097.2 vs 70.9u2009±u20097.4); and stroke volume index (29.2u2009±u20096.7 vs 33u2009±u20097.3)) and DE parameters reflecting right heart function (right ventricular (RV) end diastolic area (36.4u2009±u20095.2 vs 30.9u2009±u20098.2 cm2), left ventricular eccentricity index (1.7u2009±u20090.6 vs 1.3u2009±u20090.5), tricuspid annular planar systolic excursion (1.6u2009±u20090.5 vs 1.9u2009±u20090.2 cm)). These changes occurred without significant alteration in systemic oxygenation, heart rate, or mean systemic arterial pressure. In addition, improvements were seen in 6MWD (171u2009±u200993 vs 230u2009±u2009114), 36-Item Short Form Health Survey Mental Component Summary aggregate (38u2009±u200911 vs 44.2u2009±u200910.7), University of California, San Diego Shortness of Breath Questionnaire (87u2009±u200917.1 vs 73.1u2009±u200921), and brain natriuretic peptide (558u2009±u2009859 vs 228u2009±u2009340). Conclusions PH-targeted therapy may improve right heart haemodynamics and echocardiographic function without affecting systemic oxygen saturation in an advanced PH phenotype associated with RV dysfunction in the setting of PF.

Anastrozole in Pulmonary Arterial Hypertension. A Randomized, Double-Blind, Placebo-controlled Trial.

Rationale: The aromatase inhibitor anastrozole blocks the conversion of androgens to estrogen and blunts pulmonary hypertension in animals, but its efficacy in treating patients with pulmonary arterial hypertension (PAH) is unknown. Objectives: We aimed to determine the safety and efficacy of anastrozole in PAH. Methods: We performed a randomized, double‐blind, placebo‐controlled trial of anastrozole in patients with PAH who received background therapy at two centers. Measurements and Main Results: A total of 18 patients with PAH were randomized to anastrozole 1 mg or matching placebo in a 2:1 ratio. The two co‐primary outcomes were percent change from baseline in 17&bgr;‐estradiol levels (E2) and tricuspid annular plane systolic excursion (TAPSE) at 3 months. Anastrozole significantly reduced E2 levels compared with placebo (percent change: −40%; interquartile range [IQR], −61 to −26% vs. −4%; IQR, −14 to +4%; P = 0.003), but there was no difference in TAPSE. Anastrozole significantly increased the 6‐minute‐walk distance (median change = +26 m) compared with placebo (median change = −12 m) (median percent change: anastrozole group, 8%; IQR, 2 to 17% vs. placebo −2%; IQR, −7 to +1%; P = 0.042). Anastrozole had no effect on circulating biomarkers, functional class, or health‐related quality of life. There was no difference in adverse events. Conclusions: Anastrozole significantly reduced E2 levels in patients with PAH but had no effect on TAPSE. Anastrozole was safe, well tolerated, and improved 6‐minute‐walk distance in this small “proof‐of‐principle” study. Larger and longer phase II clinical trials of anastrozole may be warranted in patients with PAH. Clinical trial registered with www.clinicaltrials.gov (NCT 1545336).

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

Pulmonary embolism (PE) is a major cause of morbidity and mortality world-wide, and the use of thrombolytic therapy has been associated with favourable clinical outcomes in certain patient subsets. These potential benefits are counterbalanced by the risk of bleeding complications, the most devastating of which is intracranial haemorrhage (ICH). We retrospectively evaluated 9703 patients from the 2003-2012 nationwide in-patient sample database (NIS) who received thrombolytics for PE. All patients with ICH during the PE hospitalisation were identified and a clinical risk score model was developed utilizing demographics and comorbidities. The dataset was divided 1:1 into derivation and validation cohorts. During 2003-2012, 176/9705 (1.8u2009%) patients with PE experienced ICH after thrombolytic use. Four independent prognostic factors were identified in a backward logistic regression model, and each was assigned a number of points proportional to its regression coefficient: pre-existing Peripheral vascular disease (1 point), age greater than 65 years (Elderly) (1 point), prior Cerebrovascular accident with residual deficit (5 points), and prior myocardial infarction (Heart attack) (1 point). In the derivation cohort, scores of 0, 1, 2 and ≥ 5 points were associated with ICH risks of 1.2u2009%, 1.9u2009%, 2.4u2009% and 17.8u2009%, respectively. Rates of ICH were similar in the validation cohort. The C-statistic for the risk score was 0.65 (0.61-0.70) in the derivation cohort and 0.66 (0.60-0.72) in the validation cohort. A novel risk score, derived from simple clinical historical elements was developed to predict ICH in PE patients treated with thrombolytics.

Pulmonary heart disease: The heart-lung interaction and its impact on patient phenotypes

Pulmonary heart disease (PHD) refers to altered structure or function of the right ventricle occurring in association with abnormal respiratory function. Although nearly always associated with some degree of PH, the degree, nature, severity, and causality of PH in relation to the PHD is not necessarily linear and direct. Abnormal gas exchange is a fundamental underpinning of PHD, affecting pulmonary vascular, cardiac, renal, and neurohormonal systems. Direct and indirect effects of chronic respiratory disease can disrupt the right ventricular-pulmonary arterial (RV-PA) interaction and, likewise, factors such as sympathetic nervous system activation, altered blood viscosity, and salt and water retention can function in a feedback loop to further influence RV-PA function. Left heart function may also be affected, especially in those with pre-existing left heart disease. Thus, the physiologic interactions between abnormal respiratory and cardiovascular function are complex, with PHD representing a heterogeneous end organ effect of an integrated multisystem process. In this review, we propose to separate PHD into two distinct entities, “Type I” and “Type II” PHD. Type I PHD is most common, and refers to subjects with chronic respiratory disease (CRD) where the perturbations in respiratory function dominate over more mild cardiac and circulatory disruptions. In contrast, Type II PHD refers to the smaller subset of patients with more severe pulmonary vascular and right heart dysfunction, whom often present in a fashion similar to patients with PAH. Phenotypic differences are not made by PA pressure alone, but instead by differences in the overall physiology and clinical syndrome. Thus, key differences can be seen in symptomatology, physical signs, cardiac imaging, hemodynamics, and the cardiovascular and gas exchange responses to exercise. Such key baseline differences in the overall physiologic phenotype are likely critical to predicting response to PH specific therapy. Recognizing PHD as distinct phenotypes assists in the necessary distinction of these patients, and may also provide a key clinical and pathophysiologic framework for improved patient selection for future studies investigating the role of pulmonary hypertension-specific therapies in PHD.

Physical Activity and Symptoms in Pulmonary Arterial Hypertension

BACKGROUNDnFatigue is a common symptom in patients with pulmonary arterial hypertension (PAH); however, the impact of fatigue on daily physical activity in PAH is unknown. Accelerometry is a validated measure for assessing physical activity. We hypothesized that patients with PAH reporting higher levels of fatigue would have lower daily physical activity measured by accelerometry.nnnMETHODSnWe performed a prospective cohort study of 15 women with PAH. On day 1, subjects completed the Multidimensional Fatigue Inventory (MFI), the United States Cambridge Pulmonary Hypertension Outcome Review (US CAMPHOR), and a 6-min walk test. Subjects wore the accelerometer on their dominant hip and completed an activity diary for 7xa0days. On day 15, subjects repeated the MFI and the US CAMPHOR, and then wore the accelerometer and completed an activity diary for an additional 7xa0days. All multivariate analyses were adjusted for age, BMI, and PAH type.nnnRESULTSnThe mean age was 50.5 years, and 53%xa0had idiopathic or heritable PAH. During the 2xa0weeks, subjects were mostly sedentary (85%xa0of the time), although 10%xa0of their time was spent performing low-level activity. Lower average daily counts were associated with worse self-reported energy levels, whereas less day-to-day physical activity variability was associated with more self-reported mental fatigue, physical fatigue, and total activity. Higher percentage of activity bouts was also associated with worse energy.nnnCONCLUSIONSnWomen with PAH may spend most of their time being sedentary, and lower self-reported energy levels are associated with less daily activity. Interventions to improve symptoms such as fatigue may also increase physical activity levels in PAH.

Slow-paced respiration therapy to treat symptoms in pulmonary arterial hypertension

Objective To determine the feasibility of using slow‐paced respiration therapy to treat symptoms in women with pulmonary arterial hypertension (PAH). Background People with PAH report increased dyspnea, fatigue and sleep disturbance that can impair health‐related quality of life (HRQOL). Methods Ten women with PAH received 8‐weeks of daily, 15 min sessions using slow‐paced respiration therapy via the RESPeRATE™ device. Participants had baseline and follow up assessments including plasma norepinephrine and interleukin‐6 (IL‐6), self‐report questionnaires to measure dyspnea, fatigue, depressive symptoms, sleep and HRQOL along with 7‐day actigraphy and sleep diaries. Results The mean age was 50 years. Adherence to the intervention was 92%. There was decrease in median IL‐6 levels [1.3 ± 0.5 to 1.1 ± 0.4, 95% CI (0.03–0.43)] over the study period. Sleep disturbance decreased, depressive symptoms decreased and HRQOL scores decreased (higher scores indicate worse HRQOL). Conclusions In this pilot study, slow‐paced respiration therapy is feasible in patients with PAH and may improve symptoms and lower IL‐6. HighlightsA pilot study of 10 women there was 100% retention and high adherence to the 8‐week slow‐paced respiration therapy intervention.Slow‐paced respiration therapy was associated with reduced plasma IL‐6 levels and no serious adverse events occurred.Preliminary results suggest decreased wake after sleep onset, increased sleep efficiency and increased total sleep time.Depressive symptoms decreased and HRQOL scores decreased (higher HRQOL scores indicate worse HRQOL.

A ‘VIRTUAL’ ECHOCARDIOGRAPHIC SCORE FOR PREDICTING THE HEMODYNAMIC PROFILE IN PULMONARY HYPERTENSION

Differentiating PH with elevated pulmonary vascular resistance (PVR) from PH from elevated left sided filling pressure is critical. We previously developed an “Echocardiographic score” to predict hemodynamics using direct measures of chamber size, RVOT Doppler profile shape, and transmitral

Relax or Contract What's Right?

Right heart size and function at baseline and follow-up are important predictors of outcome in pulmonary arterial hypertension (PAH). The traditional imaging indicators of right heart health include metrics of right ventricular (RV) systolic function under resting conditions. Transthoracic echocardiography is commonly used; RV size and function are often qualitatively described and may be quantifiable as well. Cardiac MRI is the standard of reference for RV morphology, whereas nuclear imaging techniques were used historically and have been employed more recently to measure RV metabolism. These techniques vary in technologic complexity, necessary equipment, and required expertise, yet all generally focus on systolic function of the RV at rest.

RVOT-VTI/PASP: A NOVEL NON-INVASIVE METRIC OF PULMONARY ARTERIAL COMPLIANCE AND DIASTOLIC PRESSURE GRADIENT STATUS IN HEART FAILURE WITH PRESERVED EJECTION FRACTION

Background: Pulmonary hypertension (PH) due to heart failure with preserved ejection fraction (HFpEF) is a leading cause of PH. Within this population, the diastolic pressure gradient (DPG) distinguishes those with combined post- and pre-capillary PH (DPG ≥7 mm Hg; CpcPH), and isolated post-

Disease progression in pulmonary arterial hypertension: refining the phenotype with a prognostic biomarker profile from collagen.

Pulmonary arterial hypertension (PAH) is a progressive syndrome of right heart failure that encompasses multiple etiologies and risk factors. The presentation, clinical progression, and response to therapeutic intervention are variable across patients, and much interest has been directed in clinical