The role of rehabilitation in patients with pulmonary arterial hypertension Purpose of review The current review summarizes the latest evidence of the effects of exercise training for pulmonary hypertension patients demonstrated by six randomized controlled trails and 20 further studies. As the availability of exercise training is still limited it is important to raise awareness of the body of evidence showing the benefit for the patients and the limitations. Recent findings The effects of exercise training on exercise capacity, hemodynamics as well as quality of life are described as well as different settings and components of exercise training. Associated adverse events are critically reviewed and strategies for avoidance of these events discussed. Lastly, the most important issues of availability and reimbursement of a specialized exercise training program are examined and the future path is outlined to improve patient access. Summary The latest publications on this topic strengthen the call for international multicenter randomized controlled trials to establish the feasibility of exercise training in different healthcare systems and to enhance patient access to these programs. Correspondence to Ekkehard Grünig, Prof Dr, Centre for Pulmonary Hypertension, Thoraxklinik at Heidelberg University Hospital, Röntgenstraße 1, 69126 Heidelberg, Germany. Tel: +49 6221 396 8076; fax: +49 6221 396 1209; e-mail: ekkehard.gruenig@med.uni-heidelberg.de Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Advanced sarcoidosis Purpose of review Advanced sarcoidosis is an important cause of morbidity and mortality in sarcoidosis. Over the past few years, several studies have been published clarifying the prevalence and severity of this condition. Recent findings Pulmonary involvement is the most common form of sarcoidosis. Increased morbidity and significant mortality is encountered in advanced lung disease. Although many sarcoidosis patients with pulmonary fibrosis have a normal life expectancy, at least 20% develop progression and may die from this complication. Sarcoidosis-associated pulmonary hypertension (SAPH) is an independent cause of death in advanced pulmonary sarcoidosis. Two large multicenter registries and a large single-center report provide more details regarding presentation and outcome of SAPH. Advanced neurologic disease is associated with significant morbidity, but not much mortality. Two large retrospective reviews demonstrated the effectiveness of infliximab in treating advanced neurosarcoidosis. Advanced cardiac sarcoidosis can lead to mortality. Summary Advanced sarcoidosis is associated with significant morbidity and some mortality. Up to a quarter of all sarcoidosis patients have one or more forms of advanced disease. These patients require closer monitoring and often multiples treatments. Correspondence to Dr Robert P. Baughman, MD, Department of Medicine, University of Cincinnati Medical Center, 1001 Holmes Building, 200 Albert Sabin Way, Cincinnati, OH 45267-0565, USA. Tel: +1 513 584 5224; fax: +1 513 584 5110; e-mail: bob.baughman@uc.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Treatment of cardiac sarcoidosis Purpose of review In sarcoidosis, the appropriate management strategy remains challenging especially because of the lack of confident diagnosis, considerable variability in initial presentation, disease evolution, and outcome. Although asymptomatic patients with limited cardiac involvement have been described to have a benign outcome, cardiac sarcoidosis is associated with high morbidity and mortality and even sudden cardiac death in a significant proportion of patients. Higher morbidity and mortality can be related with both the disease activity and extent of fibrosis. Recent findings Historical series suggested a 5-year mortality rate of 60% in patients with cardiac sarcoidosis. This has definitely improved with the appropriate use of anti-inflammatory medications as well as heart failure treatment, antiarrhythmic medication and device implantation. Timely recognition and vigorous initial approach is essential in avoiding life-threatening arrhythmias and sudden cardiac death. Advanced imaging modalities have proven to be helpful in the diagnostic approach and guiding treatment decisions. However, there is no optimal screening and risk stratification strategy available and further studies are required to determine, which patients would benefit from the available treatments. Summary This review concentrates on the broad principles of management in cardiac sarcoidosis and the efficacy of sarcoidosis-specific medication and cardiac-specific therapies for cardiac dysfunction and rhythm disturbances. Correspondence to Vasileios Kouranos, PhD, Interstitial Lung Disease Unit, Royal Brompton Hospital, Sydney Street, SW3 6NP London, UK. Tel: +44 7587301300; e-mail: v.kouranos@rbht.nhs.uk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Malnutrition in pulmonary arterial hypertension: a possible role for dietary intervention Purpose of review The last decade's progress has been made in the pharmacological treatment of pulmonary arterial hypertension (PAH). The role of nutrition in relation to quality of life in this group of patients is not investigated yet. In addition to avoiding salt and high-fluid intake based on left heart failure diet, there is no evidence-based diet recommendation for PAH. Recent findings It was recently demonstrated that patients with PAH suffer from malnutrition resulting in iron and vitamin D deficiency and glucose/insulin resistance. Recent experimental studies suggest that besides reduced malabsorption of important nutrients, the microbiome of the gut is also less diverse in PAH. In this review, we summarize the current knowledge on malnutrition and dietary intake in PAH. We discuss the possible underlying mechanisms and discuss novel therapeutic interventions validated in patients with left heart failure. Summary Large-scaled studies on dietary interventions are needed in PAH. Correspondence to Anton Vonk Noordegraaf, Department of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Tel: +31 20 444 4782; fax: +31 20 444 4328; e-mail: a.vonk@amsterdamumc.nl This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The right treatment for the right ventricle Purpose of review Right ventricular (RV) function is an important determinant of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although substantial progress has been made in understanding the development of RV failure in the last decennia, this has not yet resulted in the development of RV selective therapies. In this review, we will discuss the current status on the treatment of RV failure and potential novel therapeutic strategies that are currently being investigated in clinical trials. Recent findings Increased afterload results in elevated wall tension. Consequences of increased wall tension include autonomic disbalance, metabolic shift and inflammation, negatively affecting RV contractility. Compromised RV systolic function and low cardiac output activate renin–angiotensin aldosterone system, which leads to fluid retention and further increase in RV wall tension. This vicious circle can be interrupted by directly targeting the determinants of RV wall tension; preload and afterload by PAH-medications and diuretics, but is also possibly by restoring neurohormonal and metabolic disbalance, and inhibiting maladaptive inflammation. A variety of RV selective drugs are currently being studied in clinical trials. Summary Nowadays, afterload reduction is still the cornerstone in treatment of PAH. New treatments targeting important pathobiological determinants of RV failure directly are emerging. Correspondence to Berend E. Westerhof, PhD, Department of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Tel: +31 20 444 4782; fax: +31 20 444 4328; e-mail: b.e.westerhof@amsterdamumc.nl This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Unilateral phrenic nerve stimulation in the therapeutical algorithm of central sleep apnoea in heart failure Purpose of review Central sleep apnoea (CSA) is highly prevalent in patients with heart failure and substantially impairs survival. If optimal cardiac treatment fails, alternative therapeutical options, including positive airway pressure (PAP) therapies, drugs or application of oxygen and carbon dioxide are considered to suppress CSA which interfere with the complex underlying pathophysiology. Most recently, unilateral phrenic nerve stimulation (PNS) has been studied in these patients. Therefore, there is an urgent need to critically evaluate efficacy, potential harm and positioning of PNS in current treatment algorithms. Recent findings Data from case series and limited randomized controlled trials demonstrate the feasibility of the invasive approach and acceptable peri-interventional adverse events. PNS reduces CSA by 50%, a figure comparable with continuous PAP or oxygen. However, PNS cannot improve any comorbid upper airways obstruction. A number of fatalities due to malignant cardiac arrhythmias or other cardiac events have been reported, although the association with the therapy is unclear. Summary PNS offers an additional option to the therapeutical portfolio. Intervention-related adverse events and noninvasive alternatives need clear discussion with the patient. The excess mortality in the SERVE-HF study has mainly been attributed to sudden cardiac death. Therefore, previous cardiac fatalities under PNS urge close observation in future studies as long-term data are missing. Correspondence to Winfried Randerath, MD, Professor of Medicine, Clinic for Pneumology and Allergology, Centre of Sleep Medicine and Respiratory Care, Institute of Pneumology at the University of Cologne, Bethanien Hospital, Aufderhöher Str. 169, 42699 Solingen, Germany. E-mail: randerath@klinik-bethanien.de Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Approach to tapering antisarcoidosis therapy Purpose of review Sarcoidosis is a multisystemic granulomatous disease, which commonly affects the lung. The natural course of the disease and prognosis are variable from asymptomatic, spontaneous remission to progressive disease, which requires treatment. Once treatment is initiated, tapering therapy can be problematic. Recent findings Corticosteroids are recommended as first-line therapy, but optimal regimen and duration of treatment is not well established. Treatment may differ based on severity of disease, extrapulmonary involvement, physician and patient preferences. We reviewed currently recommended regimens, particularly, in pulmonary sarcoidosis and the use of alternative treatments as corticosteroid-sparing agents. Summary Corticosteroid use is quite effective as initial therapy but is associated with significant side effects. An approach to tapering sarcoidosis therapy is not standardized, given the lack of evidence-based data. This review provides guidance based on the current literature. Correspondence to Kamonpun Ussavarungsi, MD, Division of Pulmonary and Critical Care, Department of Internal Medicine, 200 Hawkins Drive, C33 GH, Iowa City, IA 52242, USA. Tel: +1 319 384 9832; e-mail: kamonpun-ussavarungsi@uiowa.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Noninvasive volume-assured pressure support for chronic respiratory failure: a review Purpose of review Noninvasive ventilation (NIV) is an established treatment for chronic hypercapnic respiratory failure (CRF). Volume-assured pressure support (VAPS) is a mode of NIV that automatically adjusts inspiratory pressure in order to maintain a constant respiratory volume. We aim to discuss the role and application of VAPS in CRF. Recent findings Recently published meta-analyses and reviews fail to demonstrate a significant difference in gas exchange, sleep, or quality-of-life improvement in patients with CRF between VAPS and bilevel positive airway pressure (BPAP). A recent manuscript suggests that VAPS therapy in chronic obstructive pulmonary disease patients may reduce the number of exacerbations. It has been shown that with a protocol-driven approach BPAP and VAPS can both be successfully titrated during a single split-night polysomnography. Summary VAPS is as effective as other modes of NIV at improving ventilation and sleep in CRF. The potential advantage is a more consistent ventilatory support through daytime–nighttime variations and progression of disease over time. However, the impact on long-term outcomes, such as survival, has not been studied. Correspondence to Timothy I. Morgenthaler, MD, Department of Pulmonary and Critical Care Medicine and the Center for Sleep Medicine, Mayo Clinic, Rochester, MN 55905, USA. Tel: +507 266 6880; e-mail: TMorgenthaler@mayo.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Indications for treatment of sarcoidosis Purpose of review To describe the current knowledge on indications for sarcoidosis treatment. Recent findings Despite the lack of evidence-based recommendations, the sarcoidosis community has adopted the concept of starting systemic anti-inflammatory treatment because of potential danger (risk of severe dysfunction on major organs or death) or unacceptable impaired quality of life (QoL). On the contrary, while QoL and functionality are patients’ priorities, few studies have evaluated treatment effect on patient-reported outcomes. The awareness of long-term corticosteroids toxicities and consequences on QoL and the emergence of novel drugs have changed therapeutic management. Second-line therapy, mainly methotrexate and azathioprine, are indicated for corticosteroids sparing or corticosteroids-resistant sarcoidosis. TNF-α inhibitors are a useful third-line therapy in chronic refractory disease. In addition to organ-targeted treatment, efforts should also be taken for treating nonorgan-specific symptoms, such as physical training for fatigue, and various disease complications. Summary Clinicians should offer a tailored treatment for each patient and ensure a holistic multidisciplinary approach, including pharmacological and nonpharmacological interventions. Patient-centered communication is critical to drive shared decisions, in particular for the tricky situation of isolated impaired QoL as the unique therapeutic indication. Once treatment is decided, clinicians should define a clear therapeutic plan, including goals and instruments to assess response. Correspondence to Hilario Nunes, MD, PhD, Service de Pneumologie, Hôpital Avicenne, Assistance Publique Hôpitaux de Paris, 125 route de Stalingrad, Bobigny, Paris 93009, France. Tel: +33 1 48 95 51 21; fax: +33 1 48 95 51 26; e-mail: hilario.nunes@aphp.fr Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The global view Purpose of review To understand the global distribution of different forms of pulmonary hypertension. Recent findings Different registries have explored the epidemiological characteristics of pulmonary hypertension. Interestingly, there is a clear difference in the prevalence of different forms of pulmonary hypertension in developed regions in comparison with less developed countries. This finding suggests not only that extrapolation of data should be avoided but also that the known prevalence of pulmonary hypertension might be underestimated. Summary Pulmonary hypertension might be more prevalent than what is currently believed. Specific forms of pulmonary hypertension distributed worldwide might characterize an unrecognized burden that still have to be properly approached. This highlights the heterogeneity of pulmonary hypertension around the world. It is clear that more epidemiological data are still needed as well as studies addressing management alternatives in these specific regions. Correspondence to Rogerio Souza, Pulmonary Circulation Unit, Pulmonary Division, Heart Institute, University of Sao Paulo Medical School, Av. Dr Eneas de Carvalho Aguiar, 44 – 5 and – Bl 2, São Paulo, SP 05400-900, Brazil. Tel: +55 11 26 61 56 95; e-mail: rogerio.souza@fm.usp.br Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.