key: cord-0965575-dthdszdn
authors: Boukhris, Marouane; Hillani, Ali; Moroni, Francesco; Annabi, Mohamed Salah; Addad, Faouzi; Ribeiro, Marcelo Harada; Mansour, Samer; Zhao, Xiaohui; Ybarra, Luiz Fernando; Abbate, Antonio; Vilca, Luz Maria; Azzalini, Lorenzo
title: Cardiovascular implications of the COVID-19 pandemic: a global perspective
date: 2020-05-16
journal: Can J Cardiol
DOI: 10.1016/j.cjca.2020.05.018
sha: 75cf04320213a3ed0e444333d095f803065bd0ee
doc_id: 965575
cord_uid: dthdszdn

The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased utilization of healthcare services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions.

The Coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute 2 respiratory syndrome coronavirus 2 (SARS-CoV-2) [1] that infected 3,524,429 patients and 3 was linked to 247,838 deaths worldwide, as of May 4, 2020 [2] . SARS-CoV-2 infection is 4 triggered by binding to angiotensin-converting enzyme-2 (ACE2), which is highly expressed 5 in the nasopharynx and lungs, as well as in the cardiovascular system and gastrointestinal and 23 We reviewed the published literature (including multiple search strategies in 1 MEDLINE with PubMed interface) and critically assessed early reports on medRxiv 2 (https://www.medrxiv.org/). An electronic search was executed employing the keywords 3 "cardiovascular" OR "cardiac" OR "heart" AND "coronavirus 2019" OR "COVID-19" OR 4 "SARS-CoV-2", between 2019 and May 4, 2020. No language restrictions were applied. The 5 title, abstract and full text of all articles captured with these search criteria were assessed. 6 Social media (Twitter, LinkedIn, and Facebook) were also consulted. 7 In such times, methodologically-sound research on COVID-19 and its cardiovascular 8 manifestations is hampered by numerous challenges. These include SARS-CoV-2 test 9 availability and accuracy, the decision of healthcare authorities not to screen for infection 10 certain groups (which could lead to underestimation of the pandemic burden), heterogeneous 11 reporting across countries, as well as the fact that estimates of the exact incidence of specific 12 COVID-19 complications and prevalence of baseline comorbidities are often being carried out 13 in a suboptimal fashion (e.g., small single-center cohorts, isolated reports on social media, 14 etc). For all these limitations, a high degree of caution and criticism should be adopted to 15 identify selective reporting and biased data, and when drawing conclusions based on small 16 case series or anecdotal case reports. 

Epidemiology 20 SARS-CoV-2 is transmitted between people through respiratory droplets and fomites. 21 The basic reproduction number (R 0 : the number of cases one infected individual can infect on 22 average) of SARS-CoV-2 ranges from 2.2 to 3.2 [8] . However, to understand the full epidemic 23 potential of SARS-CoV-2, it is necessary to take into consideration the high fraction (up to 24 86% of cases) of undocumented infections (asymptomatic or mild symptoms) that remains 1 unrecognized and could expose a far greater portion of the population to the virus [9] . The 2 case fatality rate of COVID-19 widely varies across countries, ranging from 0.3% to 3 7.2% [10, 11] . 14 It has been speculated that some drugs could increase susceptibility to developing 15 severe forms of COVID-19. Patients with pre-existing cardiovascular disease, receiving ARB 16 or ACEI have an upregulation of ACE2, which would be therefore available in great amounts 17 to offer a binding site for SARS-CoV-2[3,4,24]. However, this concern, derived from in-vitro 18 and animal studies, has not found confirmation in clinical practice [24] . Indeed, in a large One possible mechanism of acute myocardial injury caused by SARS-CoV-2 infection 23 could be its affinity to ACE2, which is widely expressed in the heart, and cause direct 24 myocardial injury [5, 17] . Other proposed pathways include a cytokine storm triggered by an 1 imbalanced response by type 1 and type 2 T-helper cells[5], sympathetic hyperactivity, 2 anemia and hypoxemic myocardial cells damage due to respiratory dysfunction (type 2 MI). In a small meta-analysis (4 studies, 341 patients), standardized mean differences of 10 cardiac troponin I levels were significantly higher in those with severe COVID-19-related 11 symptoms compared to those with non-severe presentation [28] . Myocardial injury, present in 12 19.7% of COVID-19 patients, was associated with higher levels of inflammatory biomarkers, 13 more severe pulmonary involvement, higher need for non-invasive and invasive ventilation, In a series reporting on 68 deaths in a cohort of 150 COVID-19 patients, 7% were 23 attributed to myocarditis with hemodynamic collapse, while in 33% of cases myocarditis 24 could have played a contributing role to patient death [31] . Although the clinical picture is still 1 referred to as a "myocarditis" in many instances, myocardial infection by SARS-CoV-2 was 2 not proven in most cases with COVID-19 myocardial involvement. To date, only isolated case 3 reports provided data on the pathology of the myocardial tissue from COVID-19 patients, 

Early mortality was 39.3%. Interestingly, angiography demonstrated the absence of 22 obstructive coronary artery disease in 39.3% of cases, a finding also reported in the US by 23 Bangalore et al. [40] , who found non-obstructive disease in one-third of the patients who 24 underwent coronary angiography. In this latter series, the prognosis of STEMI presentation 1 was even worse than in the previous report, with a 72% in-hospital mortality rate.

In addition to type 2 MI, "myocarditis" and stress cardiomyopathy, microvascular 3 thrombosis has also been hypothesized as a mechanism underlying certain cases mimicking 4 STEMI presentation without obstructive coronary artery disease, given the endothelial 5 dysfunction and hypercoagulable state associated with COVID-19. Table 2 . The potential for artificial intelligence (AI) to assist in pandemic modeling and in the 6 diagnosis of COVID-19 clinical manifestations is immense. While epidemiologists and public 7 health officials cannot be replaced, AI can serve to gather and systematically organize rapidly 8 evolving information (e.g., from social media and news media) to assist officials in decision-9 making[84]. Moreover, AI is particularly suited for massive analysis of imaging data, which 10 at the moment has been taken advantage of for COVID-19 pneumonitis diagnosis[85] but is 11 also potentially suitable for cardiac applications, such as automated interpretation of 12 electrocardiograms, imaging, and pathology specimens. The COVID-19 pandemic represents the most important public health crisis of the 16 century. The health, economic, and societal impacts will be felt for many years to come. 

Common symptoms: fever, dry cough, dyspnea, myalgias, fatigue, diarrhea, anosmia, dysgeusia.

Uncommon symptoms: sputum production, headache, hemoptysis, rhinorrhea, sore throat, conjunctival injection.

Lymphopenia; prolonged prothrombin time; elevated D-dimer, alanine aminotransferase, total bilirubin and lactate dehydrogenase

PaO2/FiO2 <200 if acute respiratory distress syndrome

Generally bilateral pneumonia with multiple infiltrates and ground-grass opacity

Real-time polymerase-chain reaction (RT-PCR) assay to detect viral RNA Abbreviations: FiO2, fraction of inspired oxygen; PaO2, partial pressure of oxygen. 

-COVID-19 testing -Telemedicine -Rationalization of indications for diagnostic and therapeutic procedures -Conservative management as first-line strategy whenever possible -Minimize the number of providers per procedure -Contact and droplet precautions (gown, face mask, eye protection, gloves) for general care -N95 mask and face shield (or PAPR), waterproof gown, and gloves for aerosol-generating procedures -Surgical mask for patients with known or suspected COVID-19 -Education Cardiopulmonary resuscitation -Use of external mechanical compression devices to minimize direct contact with infected patients -Close coordination with critical care and anesthesia teams for airway management Catheterization laboratory environment -Switch to negative pressure (if possible) -Intubation prior to transfer to the catheterization laboratory (if required) Specific consideration to subspecialty care teams -Separation of individuals with overlapping skillsets to guarantee continued availability of care in case of COVID-19 infection within the team Abbreviations: PAPR, powered air-purifying respirator.

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