‘Best of CHEST journal’ session highlights top papers from 2020

The Best of CHEST Journal session at the annual meeting featured a panel of investigators who presented four of the top manuscripts, as selected by CHEST® journal editors, representing some of the most impactful research published in 2020 from the journal CHEST’s Critical Care and Pulmonary Vascular content areas.

Michele D’Alto, PhD
Michele D’Alto, PhD

Risk Reduction and Right Heart Reverse Remodeling by Upfront Triple Combination Therapy in Pulmonary Arterial Hypertension

Michele D’Alto, PhD, Chief of the Pulmonary Hypertension Center at Monaldi Hospital in Naples, Italy, reviewed the manuscript, “Risk Reduction and Right Heart Reverse Remodeling by Upfront Triple Combination Therapy in Pulmonary Arterial Hypertension” that looked at the role of triple up-front therapy, including parenteral prostanoids, for incident patients with severe pulmonary arterial hypertension (PAH).

In this retrospective study conducted at two Italian centers, Dr. D’Alto and his colleagues looked at 21 patients with newly diagnosed high-risk idiopathic PAH that was nonreversible by the inhalation of nitric oxide who were treated upfront with a combination of ambrisentan, tadalafil, and subcutaneous treprostinil between 2014 and 2018.

“We tested the safety and efficacy of this approach, looking at the hemodynamics, the right ventricular function, and risk stratification for each patient,” he said.

World Health Organization functional class, 6-min walk distance, biomarkers, echocardiography, and right-sided heart catheterization data were recorded at baseline and during follow-up.

“Triple combination therapy showed both safety and efficacy, and none of the patients stopped this treatment regimen,” Dr. D’Alto said. “We observed in an important proportion of these patients a reverse remodeling of the right ventricle, and this is very important as it ensures a much better prognosis for the patient.”

Regarding re-stratification over the course of follow-up, he said that all but one patient reached low-risk status.

“Of course, these were patients with severe PAH and no comorbidities, and we don’t know if it works also in patients with PAH due to connective tissue disease or other associated disease,” Dr. D’Alto said. “But we should stratify again and again PAH patients during follow-up, because we know the higher the risk score, the lower the survival.”


Megan Hosey, PhD
Megan Hosey, PhD

Fatigue Symptoms During the First Year Following ARDS

Megan Hosey, PhD, Assistant Professor of Physical Medicine and Rehabilitation at Johns Hopkins University, reviewed the results of “Fatigue Symptoms During the First Year Following ARDS,” which looked at the prevalence of fatigue and its association with physical, cognitive, and mental health outcomes in survivors with acute respiratory distress syndrome (ARDS).

In an analysis of data from the ARDS Network Long-Term Outcomes Study (ALTOS), the investigators evaluated associations between the validated Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) with patient and critical illness variables, and with physical, cognitive, and mental health status at 6 and 12 months following ARDS.

“At 6 months, 70% of respondents reported clinically significant levels of fatigue,” Dr. Hosey said. “At 12 months, 66% of survivors reported clinically significant fatigue and 28% noted that their fatigue was worse, while 31% reported no change, and 41% reported that they’d seen some improvement.”

At both 6 and 12 months, she said that fatigue was associated with reduced physical function and increased symptoms of psychological distress.

“Importantly, we found that 46% of patients had a significant overlap of both fatigue and self-reported ratings of physical impairment, and 27% of participants reported clinically significant fatigue overlapping with anxiety and depression scores that were also clinically significant,” Dr. Hosey said. “We believe it is important to assess fatigue in concert with both physical impairments and mental health symptoms so that we can create a multidisciplinary and multimodal treatment plan to help our patients overcome this difficult symptom.”

Ivor Douglas, MD
Ivor Douglas, MD

Fluid Response Evaluation in Sepsis Hypotension and Shock (FRESH)

Ivor Douglas, MD, Professor of Medicine at University of Colorado and Chief of Pulmonary and Critical Care Medicine at Denver Health Medical Center, discussed the results of the Fluid Response Evaluation in Sepsis Hypotension and Shock (FRESH) study, which looked at the benefit of physiologically informed fluid and vasopressor resuscitation in improving outcomes for patients with septic shock.

“There are very high levels of variability when it comes to the initial resuscitation management of patients with sepsis-associated hypotension and shock,” Dr. Douglas said. “The performance of the 3-hour sepsis bundle ranges from about 50% to as much as 100% at some hospitals. The longer it takes to complete the bundle, the higher the attributable mortality from sepsis, but in general, much of that signal for survival is driven by time to administration of antibiotics.”

This randomized clinical trial was conducted at 13 hospitals in the United States and United Kingdom and included patients who presented with sepsis that was associated with hypotension and anticipated ICU admission. Intervention arm patients were assessed for fluid responsiveness before clinically driven fluid bolus or increase in vasopressors occurred. The control arm received usual care. The primary clinical outcome was positive fluid balance at 72 hours or ICU discharge, whichever occurred first.

Among their findings, Dr. Douglas reported that fluid balance at 72 hours or upon ICU discharge was significantly lower in the intervention arm, and fewer of these patients required renal replacement therapy or mechanical ventilation.

Importantly, he said that this study reinforces the idea that “one size does not fit all” when it comes to fluid resuscitation for sepsis and that strategies to personalize the initial fluid resuscitation for patients can be informed through dynamic fluid response measurement.

“For every individual patient, there is a ‘sweet spot’ when it comes to fluid resuscitation and fluid balance,” Dr. Douglas said. “The FRESH study demonstrates that a physiologically informed approach for fluid and vasopressor resuscitation is both feasible, safe, and results in reductions in total volume administration.”

Lisa Moores, MD, FCCP
Lisa Moores, MD, FCCP

Prevention, Diagnosis, and Treatment of VTE in Patients with Coronavirus Disease 2019: CHEST Guideline and Expert Panel Report

Lisa Moores, MD, FCCP, Professor of Medicine and Associate Dean for Assessment and Professional Development at the Uniformed Services University of Health Sciences, reviewed the initial findings of an expert panel guidance report on the prevention, diagnosis, and treatment of venous thromboembolism (VTE) in patients with COVID-19.

“An article published early in the pandemic suggested that there was a decreased mortality associated with patients hospitalized with COVID-19 pneumonia who were receiving either prophylactic or systemic anticoagulation,” Dr. Moores said.

Subsequent reports, she said, confirmed a high incidence of both arterial and thrombotic events in patients with COVID-19 pneumonia.

“As more and more registries and larger cohorts were reported, we were seeing very high rates of a combination of arterial and venous events, and when you teased out the patients and excluded those that were identified purely by screening, the symptomatic event rate appeared to be higher than similarly ill cohorts without COVID-19,” Dr. Moores said.

Among the recommendations outlined in the guidance report, she said, is that all hospitalized patients with COVID-19 receive chemical thromboprophylaxis in the absence of any contraindication, such as a high bleeding risk.

“We did not feel that we had enough evidence to suggest a different approach to the dosing; however, we did favor the heparins over fondaparinux versus the direct oral anticoagulants,” Dr. Moores said. “We still don’t know enough about the underlying pathophysiology that is driving what appears to be an increased rate of venous thromboembolism, both at the macro and micro level, particularly in the ICU population. These are questions that are actively being investigated and might actually inform further versions of this panel report.”


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