COVID-19 and Heart Failure

Mandeep R. Mehra , MD, MSc, FRCP (London)

The William Harvey Distinguished Chair in Advanced Cardiovascular Medicine

Executive Director, Center for Advanced Heart Disease, Brigham and Women’s Hospital

Professor of Medicine, Harvard Medical School

Editor-in-Chief, The Journal of Heart and Lung Transplantation

Disclosures: Consultant for Abbott, Janssen, Mesoblast, Portola, Bayer, Triple Gene, Roivant, Fineheart, BICR, Leviticus and NupulseCV, Inc.

The COVID-19 Vascular Hypothesis

Stages of Clinical Disease

Siddiqi and Mehra, The Journal of Heart and Lung Transplantation 2020 39, Issue: 5, Page: 405-407

Vaduganathan et al. N Engl J Med 2020. DOI: 10.1056/NEJMsr2005760

SARS-CoV-2 and the

Renin–Angiotensin–Aldosterone System

A Vascular Twist?

Siddiqi and Mehra, The Journal of Heart and Lung Transplantation 2020 39, Issue: 5, Page: 405-407

Endothelial Cell Infection and Endotheliitis in COVID-19

Varga, Flammer, Steiger, Haberecker, Andermatt, Zinkernagel, Mehra, Schuepbach, Ruschitzka, Moch

The Lancet 2020;395:1417-1418

Sprouting and Non-Sprouting Angiogenesis

“Intussesceptive Angiogenesis”

Angiogenesis. 2014 July ; 17(3): 499–509

M Ackermann et al. N Engl J Med 2020

Microvascular Alterations in Lungs from Patients Who Died from Covid-19

Biomarkers and Endothelial Cell Function

Zhou F et al. Lancet. 2020;S0140-6736(20)30566-3

Thrombosis Cardiac Injury Inflammation

Pober, J., Sessa, W. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol 7, 803–815 (2007)

Cardiovascular Complications

• Acute cardiac injury (+Troponin, EKG or echo abnormality)

• Rates 7-22% hospitalized; ICU ~20%, non-survivors ~60%

• Heart failure/Cardiogenic Shock

• ~23% hospitalized patients; non-survivors ~52% vs survivors ~12%

• Arrhythmias of unspecified type

• 17% hospitalized; ICU patients ~44% vs non-ICU 7%

• Venous Thromboembolism – theoretic risk, incidence unknown

Zhou F et al. Lancet. 2020;S0140-6736(20)30566-3; Wang et al. JAMA. 2020;323(11):1061-1069; Shi et al. JAMA Cardiol 2020

Cardiac MRI in COVID-19

Manka, Karolyi, Polacin……………Mehra, Ruschitzka. J Heart Lung Transplant 2020 (published online)

“Myocardial Injury”

Distinct Phenotypes of Cardiac and Vascular

Presentations in COVID-19

Venous Thromboembolism in COVID-19

Annals of Internal Medicine. 6 May 2020

Zhou F et al. Lancet. 2020;S0140-6736(20)30566-3.

Complications That Kill in COVID-19

Mode of Death

Ruan et al. Intensive Care Medicine 2020

~1/3 of deaths

were cardiac

Mechanisms for Cardiac Involvement

• Direct viral toxicity

• Cardiac microvascular disease

• Hypoxia-induced myocardial injury

• Exacerbation of subclinical “Stiff Heart Syndrome”

• Stress “catecholamine-driven” Myocardial dysfunction

• Systemic inflammatory response related Cardiomyopathy

Mehra and Ruschitzka, JACC HF 2020, ahead of print

Childhood Kawasaki COVID Related Atypical Kawasaki

17 May 2020https://doi.org/10.1161/CIRCULATIONAHA.120.048360

Verdoni Lancet 2020 May 13th

Decrease Baseline Vulnerability Tackle Thrombosis Reduce Inflammation Post-recovery Care

Potential Therapeutic Candidates

• ACE Inhibitors or ARBs – Controversy resolved?

• Statins – An unusual candidate?

• Colchicine – Translate from post MI trials De Loecker I. et al. Ann. Intensive Care 2, 19 (2012).

Targeting Viral And Inflammatory Insults In A Stage

Dependent Fashion

• Effective therapy against COVID-19 illness, will require a multi-

faceted approach

• The pathophysiology of critical illness is likely related to direct viral

insult as well as a mis-directed and uncontrolled systemic immune

response that causes multi-organ injury, underlying which is

VASCULAR dysfunction and Endotheliitis

Siddiqi HK, Mehra MR. J. Heart Lung Transplant 2020

Mehra et al. NEJM 2020 May 1st

Dr. Thomas Tuttle prescribed face masks and social distancing