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Thursday, April 1, 2021

New treatments spur rethinking of what heart failure is

 Spurred by great enthusiasm for the latest treatments for heart failure, some groups are putting greater emphasis on clearly defining what exactly heart failure is, and how to communicate it to patients without demoralizing them.

There are now five classes of life-saving heart failure drugs, as angiotensin receptor-neprilysin inhibitors and SGLT2 inhibitors were added to heart failure treatment algorithms in new guidance from the American College of Cardiology (ACC).

This is an "exciting time," said Anuradha Lala, MD, of Mount Sinai Health System in New York City. "Now our efforts need to be focused on implementation, making sure that patients who will benefit from these ​medications are actually on these ​medications."

A More Comprehensive Definition of Heart Failure

As such, the new universal definition of heart failure -- drafted by the Heart Failure Society of America, European Society of Cardiology, and Japanese Heart Failure Society -- helps clarify who exactly would be eligible for which therapies and future trials according to clear cutoffs for reduced, preserved, mildly reduced, and improved ejection fraction.

There are lots of definitions of heart failure floating around, but the universal definition is more complete and accurate than any prior ones, according to Maya Guglin, MD, PhD, of Indiana University School of Medicine in Indianapolis and chair of the ACC council of heart failure and transplant as well as a reviewer for the consensus statement.

"We all pretty much agree on what heart failure is," Guglin told MedPage Today.

The new document adds the knowledge about heart failure that has been gained since the ACC and American Heart Association last defined heart failure as "a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood" in 2013 guidelines.

"Our understanding of heart failure, its pathophysiology, its prognosis ... it's evolving. It's not surprising that 7, 8 years later there was a need for another more comprehensive or more modern definition of heart failure that reflects our current understanding of the concept," Guglin said.

In particular, she cited better understanding of the greater unifying role of congestion or ventricular filling, with ejection fraction being of less importance than previously thought.

Accordingly, the universal definition of heart failure is "a clinical syndrome with symptoms and/or signs caused by a structural and or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and or objective evidence of pulmonary or systemic congestion."

'Function' Not 'Failure'

Notably, the new definition also introduces clearer, more precise language. For example, the authors favor describing heart failure that is "persistent" or "in remission" rather than "stable." Additionally, "pre-heart failure" now describes patients who have structural abnormalities but no symptoms.

The importance of word choice was highlighted by an editor's note in the Journal of Cardiac Failure by Lala and editor-in-chief Robert Mentz, MD, of Duke University Medical Center in Durham, North Carolina, published in the same issue as the new universal definition.

"Few words in the English language universally invoke the negative emotions of fear and disappointment as does the word 'failure,'" the duo wrote.

"Our introductions in the clinical space may be met with fear and disappointment, even as we provide reassurance as to advances in therapy, and attempt to instill hope for continued life with improved quality -- despite the diagnosis. Some patients prefer to not confront the notion of failure at all, and delay or avoid care all together," Lala and Mentz said.

They proposed greater adoption of the term "heart function" when communicating with patients, as is the case in Canada, for instance, where patients visit "heart function clinics."

"Our hope is that being clear on definitions ​and intentional with our words will allow for more implementation of guideline-directed medical therapy ​and best practices to improve outcomes for our patients," Lala said in an interview.

"If we move our vernacular to speaking more about 'function' and focusing on its improvement, then it could ​potentially allow for a more fruitful interaction ​and engagement between patients and their clinicians and caregivers," she said. "Focusing on 'function' allows for inclusion of speaking about prevention and lifestyle, whereas 'failure' implies in a way that we've reached some end of the spectrum that may not necessarily be addressable."

Guglin agreed with the use of "heart function" and the change in language depending on whether one is speaking to other health professionals or a layperson.

Ultimately, she emphasized, the goal is always for information to be conveyed as accurately as possible. "When it comes to patients, yes, we don't want to scare them too much, but on the other hand, you have to convey the seriousness of the issue. Otherwise, they will not take recommendations as closely to heart," she warned.

Lala acknowledged concerns that pivoting from "failure" to "function" may appear to minimize the severity of the disease.

For patients who truly have the clinical syndrome of heart failure, "I do reiterate that they have ​heart failure, ​the gravity of the disease, and that the goal is to​ institute guideline-directed therapies to facilitate a transition to heart failure in remission," she explained. "But for those patients who are not symptomatic, or were symptomatic and now feel better or whose function has improved from a variety of standpoints, incorporating the ​word ​'function' ​in our visits more and more has anecdotally been empowering."

Moving forward, it would be important to study how patients' behaviors and perceptions of their disease may change depending on how clinicians talk to them, Lala said.

"We know so many heart failure patients are referred to heart failure teams too late in the course of their disease," she noted. "If [the phrase] didn't have negative connotations, would they come earlier? Would they be​ potentially more engaged or receptive to see us? ​How would it affect their quality of life?"


Disclosures

Non-severe SARS-CoV-2 infection characterised by very early T cell proliferation

 --independent of type 1 interferon responses and distinct from other acute respiratory viruses

Aneesh ChandranJoshua RosenheimGayathrie NageswaranLeo SwaddlingGabriele PollaraRishi GuptaJose Afonso Guerra-AssuncaoAnnemarie WoolstonTahel RonelCorrina PadeJoseph GibbonsBlanca Sanz-Magallon Duque De EstradaMarc Robert de MassyMatthew WhelanAmanda SemperTim BrooksDaniel M AltmannRosemary J BoytonAine McKnightCharlotte ManistyThomas Alexander TreibelJames MoonGillian S TomlinsonMala K MainiBenjamin M ChainMahdad NoursadeghiCOVIDsortium investigators

Pathophysiology of SARS-CoV-2: Mount Sinai COVID-19 autopsy experience

 

  • Clare Bryce
  • Zachary Grimes
  • […]
  • Mary E. Fowkes 

  • PDF: https://www.nature.com/articles/s41379-021-00793-y.pdf

  • Abstract

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.

  • https://www.nature.com/articles/s41379-021-00793-y

  • J&J Statement on U.S. COVID-19 Vaccine Manufacturing

     Since January of 2020, Johnson & Johnson has been working directly with governments, health authorities and other companies to help end the global pandemic. We continue to expect to deliver our COVID-19 vaccine at a rate of more than one billion doses by the end of 2021.

    We are pleased we have met our commitment to deliver enough single-shot vaccines by the end of March to enable the full vaccination of more than 20 million people in the United States. This is part of our plan to deliver 100 million single-shot vaccines to the U.S. during the first half of 2021, aiming to deliver those doses by the end of May.

    As with the manufacturing of any complex biologic medication or vaccine, the start-up for a new process includes test runs and quality checks to ensure manufacturing is validated and the end product meets our high-quality standards. This approach includes having dedicated specialists on the ground at the companies that are part of our global manufacturing network to support safety and quality.

    This quality control process identified one batch of drug substance that did not meet quality standards at Emergent Biosolutions, a site not yet authorized to manufacture drug substance for our COVID-19 vaccine. This batch was never advanced to the filling and finishing stages of our manufacturing process.

    This is an example of the rigorous quality control applied to each batch of drug substance. The issue was identified and addressed with Emergent and shared with the United States Food & Drug Administration (FDA).

    Quality and safety continue to be our top priority. Therefore, as we continue to work with FDA and Emergent toward the Emergency Use Authorization of the Emergent Bayview Facility, Johnson & Johnson is providing additional experts in manufacturing, technical operations and quality to be on-site at Emergent to supervise, direct and support all manufacturing of the Johnson & Johnson COVID-19 vaccine. In coordination with the U.S. Department of Health & Human Services, these steps will enable us to safely deliver an additional 24 million single-shot vaccine doses through April.

    https://www.jnj.com/johnson-johnson-statement-on-u-s-covid-19-vaccine-manufacturing

    Low HDL and high triglycerides predict COVID-19 severity

     

  • Lluís Masana
  • Eudald Correig
  • Daiana Ibarretxe
  • Eva Anoro
  • Juan Antonio Arroyo
  • Carlos Jericó
  • Carolina Guerrero
  • Marcel·la Miret
  • Silvia Näf
  • Anna Pardo
  • Verónica Perea
  • Rosa Pérez-Bernalte
  • Núria Plana
  • Rafael Ramírez-Montesinos
  • Meritxell Royuela
  • Cristina Soler
  • Maria Urquizu-Padilla
  • Alberto Zamora
  • Juan Pedro-Botet on behalf of 
  • the STACOV-XULA research group

  • PDF: https://www.nature.com/articles/s41598-021-86747-5.pdf

    Abstract

    Lipids are indispensable in the SARS-CoV-2 infection process. The clinical significance of plasma lipid profile during COVID-19 has not been rigorously evaluated. We aim to ascertain the association of the plasma lipid profile with SARS-CoV-2 infection clinical evolution. Observational cross-sectional study including 1411 hospitalized patients with COVID-19 and an available standard lipid profile prior (n: 1305) or during hospitalization (n: 297). The usefulness of serum total, LDL, non-HDL and HDL cholesterol to predict the COVID-19 prognosis (severe vs mild) was analysed. Patients with severe COVID-19 evolution had lower HDL cholesterol and higher triglyceride levels before the infection. The lipid profile measured during hospitalization also showed that a severe outcome was associated with lower HDL cholesterol levels and higher triglycerides. HDL cholesterol and triglyceride concentrations were correlated with ferritin and D-dimer levels but not with CRP levels. The presence of atherogenic dyslipidaemia during the infection was strongly and independently associated with a worse COVID-19 infection prognosis. The low HDL cholesterol and high triglyceride concentrations measured before or during hospitalization are strong predictors of a severe course of the disease. The lipid profile should be considered as a sensitive marker of inflammation and should be measured in patients with COVID-19.

    https://www.nature.com/articles/s41598-021-86747-5

    SARS-CoV-2 exposure generates T-cell memory in absence of detectable viral infection

     

  • Zhongfang Wang
  • Xiaoyun Yang
  • Jiaying Zhong
  • Yumin Zhou
  • Zhiqiang Tang
  • Haibo Zhou
  • Jun He
  • Xinyue Mei
  • Yonghong Tang
  • Bijia Lin
  • Zhenjun Chen
  • James McCluskey
  • Ji Yang,


  • Alexandra J. Corbett & 
  • Pixin Ran

  • PDF: https://www.nature.com/articles/s41467-021-22036-z.pdf

    Abstract

    T-cell immunity is important for recovery from COVID-19 and provides heightened immunity for re-infection. However, little is known about the SARS-CoV-2-specific T-cell immunity in virus-exposed individuals. Here we report virus-specific CD4+ and CD8+ T-cell memory in recovered COVID-19 patients and close contacts. We also demonstrate the size and quality of the memory T-cell pool of COVID-19 patients are larger and better than those of close contacts. However, the proliferation capacity, size and quality of T-cell responses in close contacts are readily distinguishable from healthy donors, suggesting close contacts are able to gain T-cell immunity against SARS-CoV-2 despite lacking a detectable infection. Additionally, asymptomatic and symptomatic COVID-19 patients contain similar levels of SARS-CoV-2-specific T-cell memory. Overall, this study demonstrates the versatility and potential of memory T cells from COVID-19 patients and close contacts, which may be important for host protection.

    https://www.nature.com/articles/s41467-021-22036-z

    BNT162b2 Vax in People Over 80 Induces Strong Immune Response, Cross Neutralizes P.1 Brazil Variant

     

    Helen Marie Parry

    University of Birmingham - Institute of Immunology and Immunotherapy

    Gokhan Tut

    University of Birmingham

    Sian Faustini

    University of Birmingham - Clinical Immunology Service

    Christine Stephens

    University of Birmingham - Institute of Immunology and Immunotherapy

    Philip Saunders

    Quinton and Harborne PCN

    Christopher Bentley

    University of Birmingham - Institute of Immunology and Immunotherapy

    Katherine Hilyard

    Deparment of Buisness Energy and Industrial Strategy - Vaccine Taskforce

    Kevin Brown

    Public Health England

    Gayatri Amirthalingam

    Public Health England - Immunisation and Countermeasures Division

    Sue Charlton

    Public Health England - National Infection Service

    Stephanie Leung

    Government of the United Kingdom - National Infection Service

    Emily Chiplin

    Government of the United Kingdom - National Infection Service

    Naomi S. Coombes

    Government of the United Kingdom - National Infection Service

    Kevin R. Bewley

    Government of the United Kingdom - National Infection Service

    Elizabeth J. Penn

    Government of the United Kingdom - National Infection Service

    Cathy Rowe

    Public Health England

    Ashley Otter

    Public Health England

    Rosie Watts

    Government of the United Kingdom - National Infection Service

    Silvia D’Arcangelo

    Government of the United Kingdom - National Infection Service

    Bassam Hallis

    Public Health England - National Infection Service

    Andrew Makin

    Oxford Immunotec LTD

    Alex G. Richter

    University of Birmingham - Clinical Immunology Service

    Jianmin Zuo

    University of Birmingham - Institute of Immunology and Immunotherapy

    Paul Moss

    University of Birmingham - Institute of Immunology and Immunotherapy

    More...



    Background: Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials.

    Methods: We determined the serological and cellular response to spike protein in 100 people aged 80-96 years at 2 weeks after second vaccination with the Pfizer BNT162b2 mRNA vaccine.

    Findings: Antibody responses were seen in every donor with high titres in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher respectively after dual vaccination. Post-vaccine sera mediated strong neutralisation of live Victoria (Wuhan-like prototype) infection and although neutralisation titres were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective.

    Interpretation: These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 Variant of Concern.

    Funding: This work was supported by the UK Coronavirus Immunology Consortium (UK-CIC) funded by DHSC/UKRI and the National Core Studies Immunity programme.

    Declaration of Interest: None to declare