COVID-19-Related Thrombotic and Bleeding Events in Adults With Congenital Heart Disease

Flavia Fusco¹, Richard A Krasuski², Soraya Sadeghi³, Marlon S Rosenbaum⁴, Matthew J Lewis⁴, Matthew R Carazo⁵, Fred H Rodriguez⁵, Dan G Halpern⁶, Jodi L Feinberg⁶, Francisca A Galilea⁷, Fernando Baraona⁷, Ari M Cedars⁸, Jong M Ko⁸, Prashob Porayette⁹, Jennifer R Maldonado⁹, Alexandra A Frogoudaki¹⁰, Amiram Nir¹¹, Anisa Chaudhry¹², Anitha S John¹³, Arsha Karbassi¹⁴, Javier Ganame¹⁴, Arvind Hoskoppal¹⁵, Benjamin P Frischhertz¹⁶, Benjamin Hendrickson¹⁷, Carla P Rodriguez-Monserrate¹⁸, Christopher R Broda¹⁹, Daniel Tobler²⁰, David Gregg²¹, Efrén Martinez-Quintana²², Elizabeth Yeung²³, Eric V Krieger²⁴, Francisco J Ruperti-Repilado²⁵, George Giannakoulas²⁶, George K Lui²⁷, Georges Ephrem²⁸, Harsimran S Singh²⁹, Almeneisi Hasan³⁰, Heather L Bartlett³¹, Ian Lindsay³², Jasmine Grewal³³, Jeremy Nicolarsen³⁴, John J Araujo³⁵, Jonathan W Cramer³⁶, Judith Bouchardy³⁷, Khalid Al Najashi³⁸, Kristi Ryan³⁹, Laith Alshawabkeh⁴⁰, Lauren Andrade⁴¹, Magalie Ladouceur⁴², Markus Schwerzmann⁴³, Matthias Greutmann⁴⁴, Pablo Merás⁴⁵, Paolo Ferrero⁴⁶, Payam Dehghani⁴⁷, Poyee P Tung⁴⁸, Rocio Garcia-Orta⁴⁹, Rose Tompkins⁵⁰, Salwa M Gendi⁵¹, Scott Cohen⁵², Scott E Klewer⁵³, Sebastien Hascoet⁵⁴, Shailendra Upadhyay⁵⁵, Stacy D Fisher⁵⁶, Stephen Cook⁵⁷, Timothy B Cotts⁵⁸, Adrienne H Kovacs⁵⁹, Jamil A Aboulhosn³, Giancarlo Scognamiglio¹, Craig S Broberg⁵⁹, Berardo Sarubbi¹

Affiliations

¹ Adult Congenital Heart Disease Unit, Monaldi Hospital, Naples, Italy.
² Department of Cardiovascular Medicine, Duke University Health System in Durham, Durham, North Carolina, USA.
³ Ahmanson/UCLA Adult Congenital Heart Center, Los Angeles, California, USA.
⁴ Division of Cardiology, Columbia University Medical Center, New York, New York, USA.
⁵ Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA.
⁶ Division of Cardiology, New York University Langone Health, New York, New York, USA.
⁷ Instituto Nacional del Tórax - Pontificia Universidad Católica de Chile, Santiago, Chile.
⁸ Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁹ Division of Cardiology, University of Iowa Stead Family Children's Hospital, Iowa City, Iowa, USA.
¹⁰ Second Cardiology Department, ATTIKON University Hospital, Athens, Greece.
¹¹ Pediatric Cardiology and Adult Congenital Heart Disease Unit, Shaare Zedek Medical Center, Jerusalem, Israel.
¹² Penn State Hershey Heart and Vascular Institute, State College, Pennsylvania, USA.
¹³ Division of Cardiology, Children's National Hospital, Washington, District of Columbia, USA.
¹⁴ McMaster University, Hamilton, Ontario, Canada.
¹⁵ UPMC Adult Congenital Heart Disease Program, Pittsburgh, Pennsylvania, USA.
¹⁶ Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
¹⁷ Le Bonheur Heart Institute, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
¹⁸ Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
¹⁹ Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
²⁰ Division of Cardiology, University Hospital of Basel, Basel, Switzerland.
²¹ Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina, USA.
²² Cardiology Service, Universitario Insular-Materno Infantil, Las Palmas de Gran Canaria, Spain.
²³ Colorado's Adult and Teen Congenital Heart Program, Colorado University School of Medicine, Aurora, Colorado, USA.
²⁴ Division of Cardiology, University of Washington School of Medicine, Seattle, Washington, USA.
²⁵ Division of Cardiology, University Hospital Geneva, Geneva, Switzerland.
²⁶ Cardiology Department, AHEPA University Hospital, Thessaloniki, Greece.
²⁷ Division of Cardiovascular Medicine and Pediatric Cardiology, Stanford University School of Medicine, Stanford, California, USA.
²⁸ Krannert Cardiovascular Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
²⁹ Department of Medicine & Pediatrics, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York, USA.
³⁰ The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
³¹ Department of Pediatrics and Medicine, University of Wisconsin, Madison, Wisconsin, USA.
³² Division of Pediatric Cardiology, University of Utah, Salt Lake City, Utah, USA.
³³ St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
³⁴ Department of Pediatric and Adult Cardiology, Providence Adult and Teen Congenital Heart Program, Spokane, Washington, USA.
³⁵ Department of Pediatric and Adult Congenital Heart Disease, Somer Incare Cardiovascular Center, Rionegro, Colombia.
³⁶ Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
³⁷ Department of Cardiology and Cardiac Surgery, University Hospital Lausanne, Lausanne, Switzerland.
³⁸ Pediatric Cardiology Department, Prince Sultan Cardiac Center, Riyadh, Saudi Arabia.
³⁹ Adult Congenital Heart Program, OSF Healthcare Children's Hospital of Illinois, Peoria, Illinois, USA.
⁴⁰ Department of Cardiovascular Medicine, University of California-San Diego, La Jolla, California, USA.
⁴¹ Division of Cardiology, Hospital of University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁴² Adult Congenital Heart Disease Unit, Hôpital Européen Georges Pompidou, AP-HP, Université de Paris Cité, Paris, France.
⁴³ Center for Congenital Heart Disease, University Hospital Inselspital, Bern, Switzerland.
⁴⁴ Department of Cardiology, University of Zurich, Zurich, Switzerland.
⁴⁵ Cardiology Department, University Hospital La Paz, Madrid, Spain.
⁴⁶ Cardiovascular Department, ASST Papa Giovanni XXIII, University of Milano, Bergamo, Italy.
⁴⁷ Prairie Vascular Research Network, University of Saskatchewan, Regina, Saskatchewan, Canada.
⁴⁸ Division of Adult Congenital Heart Disease, University of Texas at Houston, Houston, Texas, USA.
⁴⁹ Cardiology Department, Hospital Universitario Virgen de las Nieves, Granada, Spain.
⁵⁰ The Geurin Family Congenital Heart Program, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁵¹ Adult Congenital Heart Disease Program, West Virginia University, Morgantown, West Virginia, USA.
⁵² Adult Congenital Heart Disease Program, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
⁵³ Division of Cardiology, University of Arizona, Tucson, Arizona, USA.
⁵⁴ Department of Pediatric Cardiology and Congenital Heart Disease, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
⁵⁵ Division of Pediatric Cardiology, Connecticut Children's Medical Center, Hartford, Connecticut, USA.
⁵⁶ Department of Medicine and Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁵⁷ Adult Congenital Heart Center, Helen DeVos Children's Hospital, Grand Rapids, Michigan, USA.
⁵⁸ Department of Medicine and Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
⁵⁹ Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA.

PMID: 38938489
PMCID: PMC11198511
DOI: 10.1016/j.jacadv.2023.100701

COVID-19-Related Thrombotic and Bleeding Events in Adults With Congenital Heart Disease

Flavia Fusco et al. JACC Adv. 2023.

. 2023 Nov 21;2(10):100701.

doi: 10.1016/j.jacadv.2023.100701. eCollection 2023 Dec.

Authors

Affiliations

¹ Adult Congenital Heart Disease Unit, Monaldi Hospital, Naples, Italy.
² Department of Cardiovascular Medicine, Duke University Health System in Durham, Durham, North Carolina, USA.
³ Ahmanson/UCLA Adult Congenital Heart Center, Los Angeles, California, USA.
⁴ Division of Cardiology, Columbia University Medical Center, New York, New York, USA.
⁵ Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA.
⁶ Division of Cardiology, New York University Langone Health, New York, New York, USA.
⁷ Instituto Nacional del Tórax - Pontificia Universidad Católica de Chile, Santiago, Chile.
⁸ Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁹ Division of Cardiology, University of Iowa Stead Family Children's Hospital, Iowa City, Iowa, USA.
¹⁰ Second Cardiology Department, ATTIKON University Hospital, Athens, Greece.
¹¹ Pediatric Cardiology and Adult Congenital Heart Disease Unit, Shaare Zedek Medical Center, Jerusalem, Israel.
¹² Penn State Hershey Heart and Vascular Institute, State College, Pennsylvania, USA.
¹³ Division of Cardiology, Children's National Hospital, Washington, District of Columbia, USA.
¹⁴ McMaster University, Hamilton, Ontario, Canada.
¹⁵ UPMC Adult Congenital Heart Disease Program, Pittsburgh, Pennsylvania, USA.
¹⁶ Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
¹⁷ Le Bonheur Heart Institute, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
¹⁸ Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
¹⁹ Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
²⁰ Division of Cardiology, University Hospital of Basel, Basel, Switzerland.
²¹ Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina, USA.
²² Cardiology Service, Universitario Insular-Materno Infantil, Las Palmas de Gran Canaria, Spain.
²³ Colorado's Adult and Teen Congenital Heart Program, Colorado University School of Medicine, Aurora, Colorado, USA.
²⁴ Division of Cardiology, University of Washington School of Medicine, Seattle, Washington, USA.
²⁵ Division of Cardiology, University Hospital Geneva, Geneva, Switzerland.
²⁶ Cardiology Department, AHEPA University Hospital, Thessaloniki, Greece.
²⁷ Division of Cardiovascular Medicine and Pediatric Cardiology, Stanford University School of Medicine, Stanford, California, USA.
²⁸ Krannert Cardiovascular Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
²⁹ Department of Medicine & Pediatrics, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York, USA.
³⁰ The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
³¹ Department of Pediatrics and Medicine, University of Wisconsin, Madison, Wisconsin, USA.
³² Division of Pediatric Cardiology, University of Utah, Salt Lake City, Utah, USA.
³³ St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
³⁴ Department of Pediatric and Adult Cardiology, Providence Adult and Teen Congenital Heart Program, Spokane, Washington, USA.
³⁵ Department of Pediatric and Adult Congenital Heart Disease, Somer Incare Cardiovascular Center, Rionegro, Colombia.
³⁶ Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
³⁷ Department of Cardiology and Cardiac Surgery, University Hospital Lausanne, Lausanne, Switzerland.
³⁸ Pediatric Cardiology Department, Prince Sultan Cardiac Center, Riyadh, Saudi Arabia.
³⁹ Adult Congenital Heart Program, OSF Healthcare Children's Hospital of Illinois, Peoria, Illinois, USA.
⁴⁰ Department of Cardiovascular Medicine, University of California-San Diego, La Jolla, California, USA.
⁴¹ Division of Cardiology, Hospital of University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁴² Adult Congenital Heart Disease Unit, Hôpital Européen Georges Pompidou, AP-HP, Université de Paris Cité, Paris, France.
⁴³ Center for Congenital Heart Disease, University Hospital Inselspital, Bern, Switzerland.
⁴⁴ Department of Cardiology, University of Zurich, Zurich, Switzerland.
⁴⁵ Cardiology Department, University Hospital La Paz, Madrid, Spain.
⁴⁶ Cardiovascular Department, ASST Papa Giovanni XXIII, University of Milano, Bergamo, Italy.
⁴⁷ Prairie Vascular Research Network, University of Saskatchewan, Regina, Saskatchewan, Canada.
⁴⁸ Division of Adult Congenital Heart Disease, University of Texas at Houston, Houston, Texas, USA.
⁴⁹ Cardiology Department, Hospital Universitario Virgen de las Nieves, Granada, Spain.
⁵⁰ The Geurin Family Congenital Heart Program, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁵¹ Adult Congenital Heart Disease Program, West Virginia University, Morgantown, West Virginia, USA.
⁵² Adult Congenital Heart Disease Program, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
⁵³ Division of Cardiology, University of Arizona, Tucson, Arizona, USA.
⁵⁴ Department of Pediatric Cardiology and Congenital Heart Disease, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
⁵⁵ Division of Pediatric Cardiology, Connecticut Children's Medical Center, Hartford, Connecticut, USA.
⁵⁶ Department of Medicine and Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁵⁷ Adult Congenital Heart Center, Helen DeVos Children's Hospital, Grand Rapids, Michigan, USA.
⁵⁸ Department of Medicine and Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
⁵⁹ Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA.

PMID: 38938489
PMCID: PMC11198511
DOI: 10.1016/j.jacadv.2023.100701

Abstract

Background: Altered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications.

Objectives: The purpose of this study was to investigate the prevalence and risk factors for COVID-19 TE/bleeding complications in ACHD patients.

Methods: COVID-19-positive ACHD patients were included between May 2020 and November 2021. TE events included ischemic cerebrovascular accident, systemic and pulmonary embolism, deep venous thrombosis, myocardial infarction, and intracardiac thrombosis. Major bleeding included cases with hemoglobin drop >2 g/dl, involvement of critical sites, or fatal bleeding. Severe infection was defined as need for intensive care unit, endotracheal intubation, renal replacement therapy, extracorporeal membrane oxygenation, or death. Patients with TE/bleeding were compared to those without events. Factors associated with TE/bleeding were determined using logistic regression.

Results: Of 1,988 patients (age 32 [IQR: 25-42] years, 47% male, 59 ACHD centers), 30 (1.5%) had significant TE/bleeding: 12 TE events, 12 major bleeds, and 6 with both TE and bleeding. Patients with TE/bleeding had higher in-hospital mortality compared to the remainder cohort (33% vs 1.7%; P < 0.0001) and were in more advanced physiological stage (P = 0.032) and NYHA functional class (P = 0.01), had lower baseline oxygen saturation (P = 0.0001), and more frequently had a history of atrial arrhythmia (P < 0.0001), previous hospitalization for heart failure (P < 0.0007), and were more likely hospitalized for COVID-19 (P < 0.0001). By multivariable logistic regression, prior anticoagulation (OR: 4.92; 95% CI: 2-11.76; P = 0.0003), cardiac injury (OR: 5.34; 95% CI: 1.98-14.76; P = 0.0009), and severe COVID-19 (OR: 17.39; 95% CI: 6.67-45.32; P < 0.0001) were independently associated with increased risk of TE/bleeding complications.

Conclusions: ACHD patients with TE/bleeding during COVID-19 infection have a higher in-hospital mortality from the illness. Risk of coagulation disorders is related to severe COVID-19, cardiac injury during infection, and use of anticoagulants.

Keywords: COVID-19; adult congenital heart disease; bleeding; thrombosis.

PubMed Disclaimer

Conflict of interest statement

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

**Central Illustration**
**COVID-19 Related Coagulation Disorders in ACHD Patients** Among 1,988 COVID-19 positive ACHD patients with median age of 32 (IQR: 25-42) years the incidence of coagulopathy was 1.5% and was associated with significantly higher risk of death (bottom left panel). Previous indication to anticoagulation, cardiac injury during infection and COVID-19 severity were independently associated to the risk of coagulation disorders (bottom right panel, OR and 95% CI are reported inside the bars of the bar graph). ACHD = adult patients with congenital heart disease.

See this image and copyright information in PMC

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COVID-19-Related Thrombotic and Bleeding Events in Adults With Congenital Heart Disease

Affiliations

COVID-19-Related Thrombotic and Bleeding Events in Adults With Congenital Heart Disease

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

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