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Cardiovascular Medicine and Surgery

PIONEER-HF trial: Changing practice in patients hospitalized for heart failure

Renin-angiotensin system (RAS) inhibition forms a pivotal part of guideline-recommended therapy for patients with heart failure with reduced ejection fraction (HFrEF).1 Inhibition of the neutral endopeptidase neprilysin increases levels of several vasoactive peptides that inhibit progression of HF.2 The randomized PARADIGM HF trial compared sacubitril/valsartan (angiotensin receptor neprilysin inhibition, ARNI) to enalapril in 8,434 patients with HFrEF and demonstrated a 20% reduction in the primary outcome of cardiovascular death or HF hospitalization (HR 0.80; CI 0.73– 0.87; P <.001) in patients treated with ARNI; mortality and rehospitalization were decreased significantly, as well.3 Importantly, patients had to be clinically stable and complete a sequential run-in period to be eligible for randomization. On this basis, the 2017 HF guideline update recommended transition from RAS inhibition to ARNI in trial-eligible patients.4

The recent PIONEER-HF trial now provides important evidence to support safety of careful initiation of sacubitril-valsartan for hospitalized patients with and without prior exposure to RAS.5 Hemodynamically stable patients were started on a regimen of sacubitril-valsartan, usually at doses half of those used in PARADIGM-HF. The primary endpoint of a decrease in BNP levels was improved significantly with sacubitril-valsartan (ratio 0.71, CI 0.63–0.81; P<.001), and this translated into a significant decrease in the important patient-centered secondary endpoint of rehospitalization.5 ARNI are underutilized in eligible patients; complexity of outpatient drug initiation may contribute.6

Data from this important trial suggest that clinicians should consider initiation of ARNI during hospitalization for acute heart failure. This could increase the number of patients receiving a guideline-recommended therapy that improves outcomes.

Steven M. Hollenberg, MD, FCCP

Steering Committee Chair


1. Yancy CW et al. 2013 ACCF/ AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147.

2. Vardeny O et al. Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail. 2014;2:663.

3. McMurray JJ, et al. Angiotensin– neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993.

4. Yancy CW, et al. 2017 ACC/ AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017;70:776.

5. Velasquez EJ, et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851. Epub ahead of print.

6. Luo N, et al. Early adoption of sacubitril/valsartan for patients with heart failure with reduced ejection fraction: insights from get with the guidelines-heart failure (GWTG-HF). JACC Heart Fail. 2017; 5:305.

Chest Infections

Pneumonia: It is NOW time to act!

Dr. Marcos I. Restrepo

The upper part of the globe is going through another winter season and this brings large numbers of patients visiting emergency departments and requiring admission to the hospital due to pneumonia and influenza. It is concerning to see that despite our knowledge that these events will occur during this season every year, there are no significant improvements in place compared to the prior year. But the most concerning aspect of all, is lack of perception that pneumonia and influenza remain among the most important diseases resulting in morbidity and mortality to both children and adults (GBD 2016 Lower Respiratory Infections Collaborators. Lancet Infect Dis 2018; S1473-3099[18]30310). Every year we read, listen or watch the alarming news regarding the increasing number of cases of influenza and pneumonia, the number of deaths, the lack of vaccine protection, the concerns about human-to-human transmission, the development of resistance, and the lack of resources to deal with this problem. We wonder why we tolerate this difficult situation over and over again? What can we do as a society to help fight this problem? What else needs to happen so we take this issue seriously? Why can we not improve the care of patients who suffer from pneumonia? We as part of the Chest Infections NetWork would like to raise the awareness of the pneumonia and influenza problem and unite with our communities to address this calamity once and for all! A recent editorial proposes a series of strategic solutions to address this situation that include increasing the overall resources, more funding for research, and the development of advocacy groups and education programs (Aliberti S, et al. Lancet Respir Med. 2018;S2213-2600(18):30470).

Marcos I. Restrepo, MD, MSc, PhD.

Steering Committee Vice-Chair

Clinical Research

Guidelines for the management of malignant pleural effusion

A multisociety multidisciplinary panel developed recommendations for management of malignant pleural effusions (MPE) by using the PICO (Population, Intervention, Comparator, and Outcomes) format. As per these guidelines, definitive therapy is aimed at

minimizing symptoms, re-accumulation and repeated pleural interventions, and risk of interventions in asymptomatic MPE outweighing benefits. Pleural interventions were suggested for indications such as clinical staging, obtaining molecular markers, etc. (Tremblay A. J Bronchology Interv Pulmonol. 2007;14:98). Large-volume thoracentesis is suggested for symptomatic patients and for those where lung entrapment is a concern (Lan RS. Ann Intern Med. 1997;126:768). In light of available evidence, the panel noted that the outcomes of definitive therapy for symptomatic MPE are equivocal between indwelling pleural catheter (IPC) and pleurodesis. IPC, which was restricted to un-expandable lungs in the previous guidelines, are now suggested for both expandable and un-expandable lungs (Feller-Kopman, et al. Am J Respir Crit Care Med. 2018;198[7]:839). Talc, being the most effective and widely use pleurodesis agent, is suggested to be delivered by poudrage or slurry. Higher treatment failure rates with chemical pleurodesis, as well as low Incidence rates of IPC-related cellulitis and pleural space infections, led the panel to suggest IPC for un-expanded lungs, treatment failures, and residual symptomatic loculated effusions. In patients with IPC-related infections, treatment of the infection rather than removal of the catheter was suggested unless in events where the infection failed to respond (Feller-Kopman, et al. Am J Respir Crit Care Med. 2018;198[7]:839). In view of evidence suggesting improved safety outcomes with ultrasound-guided pleural interventions (Abusedera M, et al. J Bronchology Interv Pulmonol. 2016;23:138), ultrasound guidance was recommended.

Bharat Bajantri, MD

Steering Committee Fellow-in-Training

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