01 April 2020

LIVE UPDATES from around the world: Pulmonary hypertension and COVID-19

This page is being updated regularly with the latest information on the COVID-19 pandemic with a relation to our clinics across the world. Details of how you are able to contribute to this page are found at the bottom of the article.

 

Articles

In partnership with our publisher SAGE, the PVRI and Pulmonary Circulation journal support the statement from the Wellcome Trust which calls on researchers, journals and funders to ensure that research findings and data relevant to the COVID-19 outbreak are shared rapidly and openly to inform the public health response and help save lives.

 In support of the principles set out in the statement we would like to remind authors considering submitting their article to Pulmonary Circulation that:

  • All articles accepted in Pulmonary Circulation are open access and free to read as soon as they are published.
  • Production of articles focused on COVID-19 are fast-tracked and deposited in Pubmed Central (PMC) for indexing.
  • All papers published on COVID-19 are promoted via the PVRI website and also collated on the SAGE Journals microsite for COVID-19 research.
  • We encourage authors of COVID-19 research and findings to share their findings with the WHO as early as possible.
  • Authors may post versions of their papers on institutional sites or on preprint servers before they are accepted, such as medRxiv or bioRxiv.

COVID-19 and the Heart

Posted 17 April 2020

Akbarshakh Akhmerov , Eduardo Marbán

Abstract

Infection with the novel coronavirus, SARS-CoV-2, produces a clinical syndrome known as COVID-19. When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm and elevations of cardiac injury biomarkers. Here we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects. In this rapidly moving field, this review was comprehensive as of April 3, 2020.

Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China

Posted 17 April 2020

Qing Deng, Yao Zhang, Hao Wang, Xiaoyang Zhou, Wei Hu, Yuting Cheng, Jie Yan, Haiqin Ping, Quing Zhou

Abstract

Background

A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community. Myocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients. Therefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19.

Methods

We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes. Serial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis.

Results

112 COVID-19 patients were enrolled in our study. There was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis. Most of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died. Troponin levels were significantly increased in the week preceding the death. 15 (13.4%) patients have presented signs of pulmonary hypertension. Typical signs of myocarditis were absent on echocardiography and electrocardiogram.

Conclusions

The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus. The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients.

The Globe on the Spotlight: Coronavirus Disease 2019 (Covid -19)

Posted 17 April 2020

Margarita Brida MD PhD, Massimo Chessa MD PhD, Hong Gu MD PhD, Michael A. Gatzoulis MD PhD 

Throughout history, infectious diseases represent a major global threat to human life and health, knowing neither geographic nor political borders. In 1918 the “Spanish flu” pandemic, caused by the H1N1 influenza A virus, led to catastrophic consequences with a global mortality toll of more than 50 million people (greater than the two world wars). The impact of this influenza virus was not confined to a single period ; to date, three subsequent outbreaks (1957, 1968, and 2009, the last called “ Swine flu”) resulted from descendants of the initial virus, which acquired one or more genes through reassortment.

More recently , coronaviruses (CoVs), named for the crown -like spikes on their surface, have demonstrate d similar outbreak pattern s with the Severe Acute Respiratory Syndrome Coronavirus (SARS -CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS - CoV) epidemic s in 2002 and 2012, respectively. (2, 3) The emergence of SARS -CoV and MERS -CoV underscore d the threat of cross -species transmission leading in turn to outbreaks in humans. While public health measures contained these outbreaks, scientists identified sequences of closely related SARS -like viruses circulating in bat populations , and warned of this potential future threat as early as 2015 . (4) Our world, however, failed to learn necessary lessons from the SARS -CoV and MERS -CoV outbreak s and to invest on essential global research on ways of preventin g the spread of infectious disease. History, as a result repeat s itself with the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS -CoV -2) pandemic of coronavirus disease 2019 (Covid -19).

Could pulmonary arterial hypertension (PAH) patients be at a lower risk from severe COVID-19?

Posted 14 April 2020

Evelyn M. Horn, Murali Chakinala, Ronald Oudiz, Elizabeth Joseloff, Erika B. Rosenzweig

The COVID-19 pandemic now impacts over 1.2 million individuals worldwide with higher-risk comorbidities including age, cardiac and pulmonary diseases. Pulmonary hypertension (PH) centers prepared for the worst for their high-risk PAH patients. However, providers have been surprised thus far by the paucity of hospitalized PAH-COVID-19 patients, generally tolerable symptoms in those affected, and their relatively early recovery. 

In late March, 2020, experts from over 32 U.S. PH Centers responded to a Pulmonary Hypertension Association (PHA) query. Only 13 COVID-19 cases were reported, with 1 death (Table 1), prompting us to ask, why have there been so few catastrophic COVID - PAH patient events? At the outset of the pandemic, PAH patients were warned to self-isolate, something that they may be more accustomed to than the general population, and that may be the simple answer. However, paradoxically could the preexisting pulmonary vasculopathy and/or PAH-specific medications somehow be protective for these otherwise high-risk patients? Could PH-specific medications (endothelin receptor antagonists (ERA), phosphodiesterase-5 (PDE5) inhibitors, inhaled nitric oxide (iNO), and prostacyclins) protect against some cardiopulmonary manifestations of COVID-19? Might there be an altered pulmonary endothelial response due to lack of ability to mount a florid inflammatory response, relative hypoxemia and possible effect on viral replication, efficacy of the nitric oxide/cyclic GMP pathway, antiplatelet effect of prostacyclins and/or use of anticoagulants in WSPH Group 1 PAH patients?

World Heart Federation Briefing on Prevention: Coronavirus disease 2019 (COVID-19) in low-income countries 

Posted 9 April 2020

Friedrich Thienemann , Fausto Pinto, Diederick E. Grobbee, Michael Boehm, Nooshin Bazargani, Junbo Ge, Karen Sliwa

Abstract

In December 2019, the novel coronavirus Coronavirus Disease 2019 (COVID-19) outbreak started in Wuhan, the capital of Hubei province in China. Since then it has spread to many other regions, including low-income countries.

ACE2 expression is increased in the lungs of patients with comorbidities associated with severe Covid-19

Posted 9 April 2020

Bruna GG Pinto, Antonio ER Oliveira, Youvika Singh, Leandro Jimenez, Andre NA Goncalves, Rodrigo LT Ogava, Rachel Creighton, Jean PS Peron, Helder I Nakaya

[This article is a preprint and has not been peer-reviewed. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.]

Abstract

The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in several thousand deaths worldwide in just a few months. Patients who died from Coronavirus disease 2019 (COVID-19) often had comorbidities, such as hypertension, diabetes, and chronic obstructive lung disease. The angiotensin-converting enzyme 2 (ACE2) was identified as a crucial factor that facilitates SARS-CoV2 to bind and enter host cells. To date, no study has assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analysed over 700 lung transcriptome samples of patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients, compared to control individuals. This finding suggests that patients with such comorbidities may have higher chances of developing severe COVID-19. We also found other genes, such as RAB1A, that can be important for SARS-CoV-2 infection in the lung. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. In fact, epigenetic marks found in ACE2 locus were compatible to with those promoted by KDM5B. Our systems biology approach offers a possible explanation for increase of COVID-19 severity in patients with certain comorbidities.

Call it by the correct name - pulmonary hypertension not pulmonary arterial hypertension. Growing recognition of the global health impact for a well-recognised condition and the role of the Pulmonary Vascular Research Institute

Posted 1 April 2020

Paul Corris, Werner Seeger

Abstract

May 5th signals World Pulmonary Hypertension Day and, whilst the world is currently focusing on the coronavirus pandemic, it is important to remember our patients with this condition, which continues to exert a major disease burden in all low, middle and high income countries.

Although pulmonary hypertension has long been recognised to complicate many common diseases, especially left-sided heart disease and lung disease, most basic, translational and clinical scientists together with the pharmaceutical industry have, to date, focused predominantly on pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension1. Both entities are rare, leading to the erroneous belief that pulmonary hypertension in general is a rare condition, and not worthy of major global focus.

This editorial summarises the global incidence and prevalence of pulmonary hypertension and considers implications for health-care providers, policy makers, and future research strategies.

Care of patients with pulmonary arterial hypertension during the coronavirus (COVID-19) pandemic

Posted 30 March 2020

John J Ryan, Lana Melendres, Roham Zamanian, Ronald Oudiz, Murali M. Chakinala, Erika B. Rosenzweig, Mardi Gomberg-Maitland

Abstract

The Covid-19 pandemic presents many unique challenges when caring for patients with pulmonary hypertension (PH). The Covid-19 pandemic has altered routine standard of care practice and the acute management particularly for those patients with pulmonary arterial hypertension (PAH), where PAH-specific treatments are used. It is important to balance the ongoing care and evaluation of PAH patients with “exposure risk” to Covid-19 for patients coming to clinic or the hospital. If there is a morbidity and mortality benefit from starting PAH therapies, for example in a patient with high-likelihood of PAH, then it remains important to complete the thorough evaluation. However, the Covid-19 outbreak may also represent a unique time when PH experts have to weigh the risks and benefits of the diagnostic work-up including potential exposure to Covid-19 versus initiating targeted PAH therapy in a select high-risk, high likelihood World Symposium Pulmonary Hypertension (WSPH) Group 1 PAH patients. This document will highlight some of the issues facing providers, patients and the PAH community in real-time as the Covid-19 pandemic is evolving and is intended to share expected common clinical scenarios and best clinical practices to help the community at-large.

COVID-19 General resources

World Heart Federation global study 

Posted 14 April 2020

Please contribute to the World heart Federation (WHF) global study, which aims to better describe cardiovascular outcomes and identify cardiovascular risk factors associated with poor prognosis in patients with COVID-19.

If you wish to contribute to the study, the WHF asks that you identify, if possible, at least 2 hospitals in your country who could participate. Each hospital should be able to include between 50 to 200 consecutive patients with COVID-19.

Special update on Covid-19 and PLWNCDs webinar

Published 6 April 2020

NCDA

This webinar will facilitate shared expertise on the impact of the Covid-19 pandemic on people living with NCDs (PLWNCDs), and how members of the NCDA network are responding to a heightened demand for advocacy, awareness-raising and knowledge sharing. There will be presentations from the Healthy Caribbean Coalition, Alzheimer’s Disease International, Cancer Warriors Foundation, World Health Organization (TBC), and a representative of PLWNCDs.

This webinar will be part of a shorts series for NCDA network focusing on the Covid-19 pandemic. The second webinar will focus on the impact of Covid-19 on health systems. More information will be shared with NCDA members and partners soon. 

Webinar date: 

Wednesday 15 April 2020, from 09:00-10:30 EDT // 15:00-16:30 CEST 

The Johns Hopkins Covid-19 worldwide tracker

Messages from our leadership

Werner Seeger, PVRI President

Published 7 April 2020

Dear Friends,

I hope this finds you and your loved ones safe and well. In these unprecedented times, please know that we are committed to helping you and your patients as best as we can.For this reason, we have introduced a few new online practical features:

New webpage

Entitled: Live Updates from around the world: pulmonary hypertension and Covid-19, this page will bring you regular messages from the PVRI leadership, the latest published articles and anecdotal stories on pulmonary hypertension and Covid-19, for which I encourage you to contribute.

Please follow this link for more information: https://pvrinstitute.org/en/professionals/news/2020/4/1/live-updates/

 New sponsorship application process

I am delighted to announce that the PVRI is streamlining a new sponsorship application process, which will enable you to apply for sponsorship, using a downloadable form, and receive a response from our Scientific Advisory Committee, within 4 weeks of application.

Please follow this link for more information: https://pvrinstitute.org/en/professionals/news/2020/3/30/introducing-the-new-pvri-sponsorship-application-process/

 PVRI resources

Our online learning materials and the PVRI Digital Clinic are important resources to support you. We are making every effort to ensure that the latest information is brought to you.

Keeping in touch

If you have any queries, or would like to send any contributions, please email: admin@pvrinstitute.org

Please be safe, healthy, and do not hesitate to let us know how we can help you. 

Yours sincerely, 

Werner

PVRI President 2020/21

Professor Paul Corris, Chairman, PVRI Board

Published 1 April 2020

On 1 April 2020, I returned to work undertaking a telephone-based review clinic for patients with pulmonary hypertension. I had been retired from clinical practice for two years but answered the call from the UK Government to return to work, as a volunteer, in response to the COVID 19 pandemic.

It was interesting, to say the least, and I can’t help but think that once this is all over, the way in which we conduct medicine and medical science will never return to how it was before. Face-to-face consultations, conferences and meetings will likely be reduced, in both aspects, with greater reliance on the use of tele-and-video communication. Travel will be cut down enormously.

Like many who attended the Annual World Congress in Lima, I visited the Sacred Valley and many Inca sites, via trekking on the Inca trails. The Incas had a huge respect for Mother Earth, something that we have lost in the generations that followed. COVID 19 may end up leaving a possible positive impact on climate change, particularly global warming.

That is not to trivialise the fact that COVID 19, sadly, will lead to the premature death of many in the next month or so, but it does give some stimulus for contemplation. 

One experience that seems to be emerging is that patients with PH and no other significant comorbid disease may not be at greater risk from either developing COVID 19, or at risk from it, than the normal population. It is still relatively early days, but this certainly reinforces the need to develop a registry of currently proven cases and, in due course, antibody positive cases. It will enable us to be more confident of this apparent paradox and then stimulate studies as to why that might be. The PVRI is currently working on developing this registry.

Finally, let me take the opportunity to say to our global members stay safe as you can and keep logging onto the PVRI website to keep updated with our activities.

Regards to all,

Paul

Updates from our members

Please note that all information contained within this section is purely anecdotal and should not be used for clinical decision making. 

An update from Stefano Ghio, IRCCS, Italy 

Published 22 March 2020

Overall, we have hospitalised more than 300 patients, less than 50 intubated but few with V-V ECMO. So far no one with a previous diagnosis of PAH.

In the most severe patients, we have not seen cardiogenic shock, but a few patients with (reversible) LV dysfunction due to ​coexistent sepsis. Also, a couple of patients with acute cor pulmonare precipitated by severe hypoxia.

In the less severe patients, cardiovascular involvement seems common. A substantial proportion of patients arriving with symptoms to the ER and then diagnosed as Covid+ have some a-specific ECG alterations and minor elevations of high sensitivity TNI (up to twice the normal values). We are now collecting the data.

The ECG alterations may be related to ipokaliemia, quite frequent in such patients, I do not know why. Importantly, this must be kept in mind by infectious disease colleagues, because several antiretroviral drugs may prolong QT interval.

Possibly ECG alterations and hdTNI release may be due to hypoxia (usually Covid+ patients are elderly patients, maybe having silent CAD). I have seen a patients with concomitant Tako Tsubo.

Our infectious disease colleagues have always in mind myocarditis; however, we do not have imaging data during hospitalisation of Covid to have an idea of the true prevalence of this complication. Nor we have autopsy data. No one has.

So far two young patients have had Covid myocarditis (confirmed by CMR in one case and by biopsy in another case). Not associated with LV dysfunction.

Transplantation activities are suspended in Northern Italy. There are no ICU safe enough to hospitalise patients who have undergone a recent transplantation. 

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