covid-19 and heart failure · the william harvey distinguished chair in advanced cardiovascular...
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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