Clinical trial NCT04358029: Cardiac Arrhythmias In Patients With Coronavirus Disease (COVID-19)
Official title: Cardiac Arrhythmias In Patients With Coronavirus Disease (COVID-19)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID 19 Cardiac
COVID 16 Arrhythmia
COVID 19 Death
Keywords: COVID 19 Cardiac
Cardiac Arrhythmias COVID
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2020-04-22
Enrollment: 4000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who have been diagnosed with COVID-19 infection at Mount Sinai Hospital will be included.

Brief summary: The objective of the study is to estimate the frequency of cardiac arrhythmias and characterize the mode of death in patients with coronavirus disease (SARS-CoV-2; COVID-19). The study will also evaluate the long term cardiac outcomes in patients previously diagnosed with COVID-19.

This is a single-center, retrospective/ prospective registry enrolling all COVID-19 positive patients at Mount Sinai Hospital.

Cohort 1:

Retrospective chart review:

1. Patients who have been diagnosed with COVID-19 infection at Mount Sinai Hospital will be included.
2. A cohort of 1000 influenza patients will also be evaluated for purpose of comparison.

Cohort 2:

Prospective data collection of 100 patients who:

1. Were hospitalized for COVID-19 and who had an abnormal echocardiogram during hospitalization.
2. A matched cohort (for age, gender, troponin level, and days since hospital discharge) who did not have abnormalities on their echocardiograms (or who did not undergo echocardiogram) to ascertain that in this unusual disease, subjects did not develop echo abnormalities following hospital discharge.

Detailed description: STUDY OBJECTIVE The objective of the study is to estimate the frequency of cardiac arrhythmias and characterize the mode of death in patients with the novel coronavirus disease (SARS-CoV-2; COVID-19). The study will also evaluate the long term cardiac outcomes in patients previously diagnosed with COVID-19.

INTRODUCTION, RATIONALE The novel coronavirus (SARS-CoV-2) emerged in Wuhan, China, in late 2019 and has quickly become a pandemic, significantly impacting the health and economy of the United States and the rest of the world. There are over 500,000 cases and 24,000 deaths related to COVID-19 worldwide, with an estimated mortality rate ranging from 1-8%. The United States has been impacted by this pandemic significantly with over 80,000 cases and thousands of deaths reported; these numbers will continue to worsen.

Patients infected with COVID-19 can exhibit a wide range of clinical manifestations, ranging from an asymptomatic state to mild upper respiratory symptoms (with low-grade fever) to severe disease with hypoxia and acute respiratory distress syndrome (ARDS) type lung injury. In the setting of hypoxemic respiratory failure, ground glass opacification on chest imaging is found more than 50% of the time.

COVID-19 has the potential to cause myocardial injury with at least 17% found to have an elevated troponin and 23% noted to have heart failure in a study of 191 inpatients from Wuhan, China. The prevalence of heart failure was significantly higher among non-survivors compared with survivors (52% vs. 12%). In a meta-analysis of 4 studies including a total of 341 patients, standardized mean difference of cardiac troponin I levels were significantly higher in those with severe COVID-19 related illness compared to those with non-severe disease (25.6, 95% CI 6.8-44.5). Furthermore, cases of fulminant myocarditis with cardiogenic shock have also been reported, with associated atrial and ventricular arrhythmias. In a recent report from Wuhan, China, 16.7% of hospitalized and 44.4% of ICU patients with COVID-19 had cardiac arrhythmias. Given the potential sampling bias in sicker, hospitalized patients with hypoxia and electrolyte abnormalities in the acute phase of severe illness can potentiate cardiac arrhythmias, the exact arrhythmic risk related to COVID-19 in patients with less severe illness or those who recover from the acute phase of the severe illness is currently unknown.

Furthermore, as it is currently unclear what medications may be beneficial for patients with COVID-19. Several medications eg: chloroquine, hydroxychloroquine, remdesivir, tocilizumab etc. are currently being investigated. Hydroxychloroquine is known to block Kv11.1 (HERG) and can cause drug-induced LQT. As such, these drugs are used concomitantly with other antiarrhythmic drugs such as amiodarone, Tikosyn, sotalol etc. which can be associated with QT prolongation requiring close EKG and cardiac monitoring. Improved characterization of arrhythmia burden and mechanism of death is critical, primarily in guiding the need for developing treatment strategies, additional arrhythmia monitoring and need to consider advanced prevention strategies including the role of implantable cardioverter defibrillator (ICD).

Eligibility criteria: Inclusion Criteria:

Cohort 1 (Retrospective):

1. Patients who have been diagnosed with COVID-19 infection at Mount Sinai Hospital will be included.
2. A cohort of 1000 influenza patients will also be evaluated for purpose of comparison.

Cohort 2 (Prospective) up to 100 patients who:

1. Were hospitalized for COVID-19 and who had an abnormal echocardiogram (\~50 patients), defined as:

   1. Abnormal Left Ventricular function ( regional or global)
   2. Abnormal Right Ventricular function
   3. Pericardial effusion
   4. Diastolic dysfunction III-IV
2. A matched cohort (\~50 patients, matched for age, gender, troponin level, and days since hospital discharge) who did not have abnormalities on their echocardiograms (or who did not undergo echocardiogram) to ascertain that in this unusual disease, subjects did not develop echo abnormalities following hospital discharge

Exclusion Criteria :

1. Retrospective: Individuals who have not been diagnosed with COVID-19 nor influenza.
2. Prospective: a.) Individuals who have not been diagnosed with COVID-19 b.) subjects under the age of 18 years. c.) unwilling or unable to sign consent. d.) residing in a long term care facility and unable to attend follow-up visit at MS. e.) no follow up visit conducted post-COVID hospitalization.

Primary outcomes:
measure: Frequency of cardiac arrhythmias
timeFrame: 19 Months
Secondary outcomes:
measure: Mode of death
timeFrame: 19 Months
measure: Number of recurrence of atrial arrhythmias
timeFrame: 19 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Vivek Reddy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Martin Goldman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases. (2020, April 17). CDC: Cases of Coronavirus Disease (COVID-19) in the U.S. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fcases-in-us.html
citation: World Health Organization. (2020, April 20). WHO: Coronavirus 2019 Situation Reports. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/
citation: Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.
citation: Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, Spitters C, Ericson K, Wilkerson S, Tural A, Diaz G, Cohn A, Fox L, Patel A, Gerber SI, Kim L, Tong S, Lu X, Lindstrom S, Pallansch MA, Weldon WC, Biggs HM, Uyeki TM, Pillai SK; Washington State 2019-nCoV Case Investigation Team. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020 Mar 5;382(10):929-936. doi: 10.1056/NEJMoa2001191. Epub 2020 Jan 31.
citation: Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.
citation: Lippi G, Lavie CJ, Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis. Prog Cardiovasc Dis. 2020 May-Jun;63(3):390-391. doi: 10.1016/j.pcad.2020.03.001. Epub 2020 Mar 10. No abstract available.
citation: Hu H, Ma F, Wei X, Fang Y. Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin. Eur Heart J. 2021 Jan 7;42(2):206. doi: 10.1093/eurheartj/ehaa190. No abstract available.
citation: Liu K, Fang YY, Deng Y, Liu W, Wang MF, Ma JP, Xiao W, Wang YN, Zhong MH, Li CH, Li GC, Liu HG. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl). 2020 May 5;133(9):1025-1031. doi: 10.1097/CM9.0000000000000744.
citation: Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.
citation: Traebert M, Dumotier B, Meister L, Hoffmann P, Dominguez-Estevez M, Suter W. Inhibition of hERG K+ currents by antimalarial drugs in stably transfected HEK293 cells. Eur J Pharmacol. 2004 Jan 19;484(1):41-8. doi: 10.1016/j.ejphar.2003.11.003.
citation: Turagam MK, Musikantow D, Goldman ME, Bassily-Marcus A, Chu E, Shivamurthy P, Lampert J, Kawamura I, Bokhari M, Whang W, Bier BA, Malick W, Hashemi H, Miller MA, Choudry S, Pumill C, Ruiz-Maya T, Hadley M, Giustino G, Koruth JS, Langan N, Sofi A, Dukkipati SR, Halperin JL, Fuster V, Kohli-Seth R, Reddy VY. Malignant Arrhythmias in Patients With COVID-19: Incidence, Mechanisms, and Outcomes. Circ Arrhythm Electrophysiol. 2020 Nov;13(11):e008920. doi: 10.1161/CIRCEP.120.008920. Epub 2020 Oct 7.