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Id Subject Object Predicate Lexical cue
T1 0-35 Sentence denotes Cardiovascular disease and COVID-19
T2 37-45 Sentence denotes Abstract
T3 46-65 Sentence denotes Background and aims
T4 66-230 Sentence denotes Many patients with coronavirus disease 2019 (COVID-19) have underlying cardiovascular (CV) disease or develop acute cardiac injury during the course of the illness.
T5 231-356 Sentence denotes Adequate understanding of the interplay between COVID-19 and CV disease is required for optimum management of these patients.
T6 358-365 Sentence denotes Methods
T7 366-478 Sentence denotes A literature search was done using PubMed and Google search engines to prepare a narrative review on this topic.
T8 480-487 Sentence denotes Results
T9 488-601 Sentence denotes Respiratory illness is the dominant clinical manifestation of COVID-19; CV involvement occurs much less commonly.
T10 602-741 Sentence denotes Acute cardiac injury, defined as significant elevation of cardiac troponins, is the most commonly reported cardiac abnormality in COVID-19.
T11 742-791 Sentence denotes It occurs in approximately 8–12% of all patients.
T12 792-971 Sentence denotes Direct myocardial injury due to viral involvement of cardiomyocytes and the effect of systemic inflammation appear to be the most common mechanisms responsible for cardiac injury.
T13 972-1057 Sentence denotes The information about other CV manifestations in COVID-19 is very limited at present.
T14 1058-1256 Sentence denotes Nonetheless, it has been consistently shown that the presence of pre-existing CV disease and/or development of acute cardiac injury are associated with significantly worse outcome in these patients.
T15 1258-1269 Sentence denotes Conclusions
T16 1270-1374 Sentence denotes Most of the current reports on COVID-19 have only briefly described CV manifestations in these patients.
T17 1375-1648 Sentence denotes Given the enormous burden posed by this illness and the significant adverse prognostic impact of cardiac involvement, further research is required to understand the incidence, mechanisms, clinical presentation and outcomes of various CV manifestations in COVID-19 patients.
T18 1650-1660 Sentence denotes Highlights
T19 1661-1776 Sentence denotes • COVID-19 is primarily a respiratory illness but cardiovascular involvement can occur through several mechanisms.
T20 1777-1890 Sentence denotes • Acute cardiac injury is the most reported cardiovascular abnormality in COVID-19, with average incidence 8-12%
T21 1891-2018 Sentence denotes • Underlying CVD and/or development of acute cardiac injury are associated with significantly worse outcome in these patients.
T22 2019-2103 Sentence denotes • Information about other cardiovascular manifestations is very limited at present.
T23 2105-2120 Sentence denotes 1 Introduction
T24 2121-2326 Sentence denotes The emergence of novel coronavirus, officially known as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has presented an unprecedented challenge for the healthcare community across the world.
T25 2327-2531 Sentence denotes High infectivity, ability to get transmitted even during asymptomatic phase and relatively low virulence have resulted in rapid transmission of this virus beyond geographic regions, leading to a pandemic.
T26 2532-2676 Sentence denotes The first case of this disease, known as coronavirus disease 2019 (COVID-2019), occurred on December 8, 2019 in the Hubei province of China [1].
T27 2677-2919 Sentence denotes Since then, within a short span of just over 3 months, the infection has spread to 177 countries/area/territories across the world, with 266073 confirmed cases and 11184 deaths (World Health Organization statistics as on March 21, 2020) [2] .
T28 2920-2985 Sentence denotes Table 1 Cardiovascular complications in coronavirus disease 2019.
T29 2986-3017 Sentence denotes Manifestation Incidence Remarks
T30 3018-3216 Sentence denotes Acute cardiac injury∗ (most commonly defined as elevation of cardiac troponin I above 99th percentile upper reference limit) 8–12% on average [10] • Most commonly reported cardiovascular abnormality
T31 3217-3292 Sentence denotes • Can result from any of the following mechanisms-•Direct myocardial injury
T32 3293-3315 Sentence denotes •Systemic inflammation
T33 3316-3357 Sentence denotes •Myocardial oxygen demand supply mismatch
T34 3358-3379 Sentence denotes •Acute coronary event
T35 3380-3391 Sentence denotes •Iatrogenic
T36 3392-3425 Sentence denotes • Strong adverse prognostic value
T37 3426-3563 Sentence denotes Acute coronary event Not reported, but appears to be low Potential mechanisms-• Plaque rupture due to inflammation/increased shear stress
T38 3564-3617 Sentence denotes • Aggravation of pre-existing coronary artery disease
T39 3618-3784 Sentence denotes Left ventricular systolic dysfunction Not reported Any of the causes of myocardial dysfunction mentioned above can lead to acute left ventricular systolic dysfunction
T40 3785-3989 Sentence denotes Heart failure Reported in one study- 52% in those who died, 12% in those who recovered and were discharged [5] • Any of the causes of myocardial dysfunction mentioned above can lead to acute heart failure
T41 3990-4108 Sentence denotes • Increased metabolic demand of a systemic disease can cause acute decompensation of pre-existing stable heart failure
T42 4109-4263 Sentence denotes Arrhythmia 16.7% overall; 44.4 in severe illness, 8.9% in mild cases [8] Both tachyarrhythmia and bradyarrhythmia can occur but exact nature not described
T43 4264-4369 Sentence denotes Potential long-term consequences Too early to assess Too early to ascertain for coronavirus disease 2019.
T44 4370-4578 Sentence denotes However, patients recovering from a similar earlier illness- Severe Acute Respiratory Syndrome- continued to have long-term abnormalities of lipid and glucose metabolism and of cardiovascular homeostasis [12]
T45 4579-4809 Sentence denotes ∗ Acute cardiac injury is a non-specific term with significant overlap with other cardiovascular manifestations; however, it is listed here because of how reporting has been done in most of the studies on coronavirus disease 2019.
T46 4810-5003 Sentence denotes Respiratory involvement, presenting as mild flulike illness to potentially lethal acute respiratory distress syndrome or fulminant pneumonia, is the dominant clinical manifestation of COVID-19.
T47 5004-5158 Sentence denotes However, much like any other respiratory tract infection, pre-existing cardiovascular disease (CVD) and CV risk factors enhance vulnerability to COVID-19.
T48 5159-5254 Sentence denotes Further, COVID-19 can worsen underlying CVD and even precipitate de novo cardiac complications.
T49 5255-5364 Sentence denotes This review is aimed at providing overview of various CV manifestations in patients presenting with COVID-19.
T50 5365-5489 Sentence denotes The impact of pre-existing CVD and new onset cardiac complications on clinical outcomes in these patients is also discussed.
T51 5490-5784 Sentence denotes Since our understanding on this subject is only evolving at this stage, the information contained in the subsequent text is based mainly on the limited early experience with COVID-19 and learnings from the previous coronavirus illnesses, namely SARS and Middle-East Respiratory Syndrome (MERS).
T52 5786-5803 Sentence denotes 2 Search methods
T53 5804-6029 Sentence denotes A literature search was done using PubMed and Google search engines for original and review articles, advisories from professional societies, and expert commentaries published since the onset of the current COVID-19 epidemic.
T54 6030-6201 Sentence denotes Search terms “COVID-19” and “coronavirus” were used in combination with “cardiac”, “cardiovascular”, “arrhythmia”, “myocardial infarction”, “troponin” and “heart failure”.
T55 6202-6288 Sentence denotes Relevant cross-references for previous studies about SARS and MERS were also reviewed.
T56 6290-6320 Sentence denotes 2.1 Pathogenic considerations
T57 6321-6384 Sentence denotes SARS-CoV-2 is caused by a novel enveloped RNA beta-coronavirus.
T58 6385-6614 Sentence denotes Seven species of these beta-coronaviruses are known to cause human infections, with four mainly causing mild flulike symptoms and the remaining three resulting in potentially fatal illnesses (SARS, MERS and the ongoing COVID-19).
T59 6615-6733 Sentence denotes Although respiratory tract is the primary target for SARS-CoV-2, CV system may get involved in several different ways.
T60 6734-6823 Sentence denotes Following are the common mechanisms responsible for CV complications in COVID-19 [3,4]-1.
T61 6825-7012 Sentence denotes Direct myocardial injury- SARS-CoV-2 enters human cells by binding to angiotensin-converting enzyme 2 (ACE2), a membrane bound aminopeptidase which is highly expressed in heart and lungs.
T62 7013-7140 Sentence denotes ACE2 plays an important role in neurohumoral regulation of CV system in normal health as well as in various disease conditions.
T63 7141-7278 Sentence denotes The binding of SARS-CoV-2 to ACE2 can result in alteration of ACE2 signaling pathways, leading to acute myocardial and lung injury [3,4].
T64 7279-7281 Sentence denotes 2.
T65 7283-7490 Sentence denotes Systemic inflammation- More severe forms of COVID-19 are characterized by acute systemic inflammatory response and cytokine storm, which can result in injury to multiple organs leading to multiorgan failure.
T66 7491-7611 Sentence denotes Studies have shown high circulatory levels of proinflammatory cytokines in patients with severe/critical COVID-19 [5,6].
T67 7612-7614 Sentence denotes 3.
T68 7616-7877 Sentence denotes Altered myocardial demand-supply ratio- Increased cardiometabolic demand associated with the systemic infection coupled with hypoxia caused by acute respiratory illness can impair myocardial oxygen demand-supply relationship and lead to acute myocardial injury.
T69 7878-7880 Sentence denotes 4.
T70 7882-8087 Sentence denotes Plaque rupture and coronary thrombosis- Systemic inflammation as well as increased shear stress due to increased coronary blood flow can precipitate plaque rupture resulting in acute myocardial infarction.
T71 8088-8169 Sentence denotes Prothrombotic milieu created by systemic inflammation further increases the risk.
T72 8170-8172 Sentence denotes 5.
T73 8174-8351 Sentence denotes Adverse effects of various therapies- Various antiviral drugs, corticosteroids and other therapies aimed at treating COVID-19 can also have deleterious effects on the CV system.
T74 8352-8354 Sentence denotes 6.
T75 8356-8525 Sentence denotes Electrolyte imbalances- Electrolyte imbalances can occur in any critical systemic illness and precipitate arrhythmias, esp. in patients with underlying cardiac disorder.
T76 8526-8664 Sentence denotes There is particular concern about hypokalemia in COVID-19, due to interaction of SARS-CoV-2 with renin-angiotensin-aldosterone system [7].
T77 8665-8729 Sentence denotes Hypokalemia increases vulnerability to various tachyarrhythmias.
T78 8731-8772 Sentence denotes 2.1.1 Role of underling CV comorbidities
T79 8773-8944 Sentence denotes The patients with pre-existing CVD appear to have heightened vulnerability to develop COVID-19 and tend to have more severe disease with worse clinical outcomes [1,4,6,8].
T80 8945-9097 Sentence denotes Various CV risk factors also adversely affect porgnosis of these patients, although they do not seem to increase likleihood of developing the infection.
T81 9098-9308 Sentence denotes A meta-analysis of six published studies from China including 1527 patients with COVID-19 reported 9.7%, 16.4% and 17.1% prevalence of diabetes, cardio-cerebrovascular disease and hypertension respectively [4].
T82 9309-9497 Sentence denotes Although the prevalence of diabetes and hypertension in this cohort was same as in the Chinese general population, the prevalence of cardio-cerebrovascular disease was considerably higher.
T83 9498-9771 Sentence denotes More importantly, the presence of diabetes, cardio-cerebrovascular disease and hypertension was associated with a 2-fold, 3-fold and 2-fold greater risk of severe disease or requiring intensive care unit (ICU) admission, suggesting prognostic impact of these comorbidities.
T84 9772-9921 Sentence denotes A much larger report from the Chinese Center for Disease Control and Prevention described clinical outcomes in 44672 confirmed cases of COVID-19 [1].
T85 9922-10096 Sentence denotes The overall case fatality rate (CFR) was 2.3% in the entire cohort but significantly higher (6%, 7.3% and 10.5% respectively) in patients with hypertension, diabetes and CVD.
T86 10097-10268 Sentence denotes Although data is lacking, the prevalence of various CV comorbidities and their impact on clinical outcomes seem to vary considerably across different geographic locations.
T87 10269-10396 Sentence denotes The CFRs have been lower in China outside Hubei province and many other countries but much higher in some European nations [2].
T88 10397-10519 Sentence denotes A small report including 21 patients from Washington, United States of America presented a particularly grim scenario [9].
T89 10520-10631 Sentence denotes Comorbidities were common in this cohort, with diabetes present in 33.3% and congestive heart failure in 42.9%.
T90 10632-10709 Sentence denotes Acute cardiac dysfunction occurred in 33.3% patients and 52.4% patients died.
T91 10710-10949 Sentence denotes However, the overall CFR in the United States seems to be much lower (201 deaths out of 15219 confirmed cases) [2], although it is likely to rise as many of the patients are currently hospitalized and have not yet had the definite outcome.
T92 10951-10997 Sentence denotes 2.2 Cardiovascular manifestations of COVID-19
T93 10999-11029 Sentence denotes 2.2.1 Acute myocardial injury
T94 11030-11123 Sentence denotes Acute myocardial injury is the most commonly described CV complication in COVID-19 (Table 1).
T95 11124-11315 Sentence denotes Different reports have used different definitions for acute myocardial injury, including rise in cardiac enzymes (different biomarkers and cut-offs) and/or electrocardiographic abnormalities.
T96 11316-11472 Sentence denotes However, an elevation of high-sensitivity cardiac troponin I (cTnI) above 99th percentile upper reference limit is the most commonly used definition.Table 1
T97 11473-11633 Sentence denotes The overall incidence of acute cardiac injury has been variable but roughly 8–12% of the positive cases are known to develop significant elevation of cTnI [10].
T98 11634-11903 Sentence denotes The aforementioned meta-analysis of the Chinese studies [4] reported 8% incidence of acute cardiac injury whereas another study including only those patients who had had a definite outcome (death or discharge from hospital) reported 17% incidence of cTnI elevation [5].
T99 11904-12065 Sentence denotes Regardless of the actual incidence, acute cardiac injury has been consistently shown to be a strong negative prognostic marker in patients with COVID-19 [5,6,8].
T100 12066-12184 Sentence denotes The patients admitted to ICU or having severe/fatal illness have several-fold higher likelihood of troponin elevation.
T101 12185-12323 Sentence denotes In contrast, the incidence of elevated troponin has been very low (only 1–2%) in patients having mild illness not requiring ICU admission.
T102 12324-12451 Sentence denotes Any of the mechanisms described above can lead to acute cardiac injury and rise in cardiac troponins in patients with COVID-19.
T103 12452-12676 Sentence denotes The relative role of these different mechanisms has not been described but direct (i.e. non-coronary) myocardial injury due to viral myocarditis or the effect of systemic inflammation appear to be the most common mechanisms.
T104 12677-12813 Sentence denotes These observations are supported by a previous autopsy study in patients who had died due to SARS during the Toronto SARS outbreak [11].
T105 12814-12975 Sentence denotes In this study, the viral ribonucleic acid was detected in 35% of the autopsied human heart samples, providing evidence for direct myocardial injury by the virus.
T106 12976-13097 Sentence denotes No study has described the incidence of ST-segment elevation myocardial infarction in COVID-19, but it appears to be low.
T107 13098-13247 Sentence denotes Similarly, the incidence of left ventricular systolic dysfunction, acute left ventricular failure and cardiogenic shock have also not been described.
T108 13248-13332 Sentence denotes Only one Chinese study reported incidence of heart failure in COVID-19 patients [5].
T109 13333-13470 Sentence denotes Heart failure had occurred in 52% of the patients who subsequently died and in 12% of the patients who were discharged from the hospital.
T110 13472-13490 Sentence denotes 2.2.2 Arrhythmias
T111 13491-13556 Sentence denotes Both tachy- and brady-arrhythmias are known to occur in COVID-19.
T112 13557-13687 Sentence denotes A study describing clinical profile and outcomes in 138 Chinese patients with COVID-19 reported 16.7% incidence of arrhythmia [8].
T113 13688-13815 Sentence denotes The incidence was much higher (44.4%) in those requiring ICU admission as compared to those not requiring ICU admission (8.9%).
T114 13816-13857 Sentence denotes The type of arrhythmia was not described.
T115 13859-13898 Sentence denotes 2.2.3 Potential long-term consequences
T116 13899-14037 Sentence denotes COVID-19 has emerged only a few months ago and it is too early to predict long-term outcome of the patients who recover from this illness.
T117 14038-14195 Sentence denotes However, some important messages can be gleaned from previous experiences with SARS, caused by SARS-CoV which shares considerable similarity with SARS-CoV-2.
T118 14196-14420 Sentence denotes It was reported that among patients who had recovered from SARS, 68% continued to have abnormalities of lipid metabolism at 12-years follow-up; CV abnormalities were present in 40% and altered glucose metabolism in 60% [12].
T119 14421-14530 Sentence denotes Similar findings have also been reported in patients recovering from other respiratory tract infections [13].
T120 14531-14734 Sentence denotes Considering this, careful follow-up of those recovering from the current COVID-19 would be important to understand the long-term impact of this illness and also to protect these patients from future CVD.
T121 14736-14764 Sentence denotes 2.3 Management implications
T122 14765-14946 Sentence denotes The overall management principles for patients presenting with COVID-19 who develop CV complications or who have pre-existing CVD are same as for any other patient without COVID-19.
T123 14947-15015 Sentence denotes However, there are a few important points that need consideration-1.
T124 15016-15136 Sentence denotes As caregivers, it is our utmost responsibility to protect ourselves from getting infected while managing these patients.
T125 15137-15261 Sentence denotes Therefore, all heathcare personnel engaged in the care of COVID-19 patients must observe necessary precautions at all times.
T126 15262-15412 Sentence denotes All of them should be trained in donning, usage, and doffing of the personal protective equipment in accordance with the existing practice guidelines.
T127 15413-15415 Sentence denotes 2.
T128 15416-15576 Sentence denotes The hospital systems need to ensure preparedness for dealing with large volume of COVID-19 patients, many of whom would need ICU care and/or acute cardiac care.
T129 15577-15736 Sentence denotes Appropriate protocols for rapid diagnosis, triage, isolation, and management of COVID-19 patients with CV complications should be developed and well-rehearsed.
T130 15737-15905 Sentence denotes Rapid triaging and management of these patients is crucial, not only to allow efficient utilization of healthcare resources but also to minimize exposure to caregivers.
T131 15906-16060 Sentence denotes There are already reports highlighting delays in delivering acute cardiac care due to extra precautions that need to be observed in view of COVID-19 [14].
T132 16061-16108 Sentence denotes Efforts should be made to minimize such delays.
T133 16109-16111 Sentence denotes 3.
T134 16112-16252 Sentence denotes Strong emphasis should be placed on avoiding unwarranted diagnostic tests (e.g. cardiac troponin, echocardiography, etc.) in these patients.
T135 16253-16486 Sentence denotes This is required to minimize unwarranted downstream diagnostic/therapeutic procedures which would further strain the already stretched healthcare resources and would also subject caregivers to added risk of exposure to the infection.
T136 16487-16649 Sentence denotes The American College of Cardiology has released an advisory discouraging random measurement of cardiac biomarkers such as troponins and natriuretic peptides [15].
T137 16650-16814 Sentence denotes It urges all the clinicians to reserve these assays for circumstances in which they would actually meaningfully add to the management of the patients with COVID-19.
T138 16815-16952 Sentence denotes The American Society of Echocardiography has also issued a similar advisory regarding the use of echocardiography in these patients [16].
T139 16953-16955 Sentence denotes 4.
T140 16956-17167 Sentence denotes The individual hospitals may also have to reconsider risk-benefit ratio of primary percutaneous intervention vs fibrinolysis in patients with COVID-19 who present with ST-segment elevation myocardial infarction.
T141 17168-17170 Sentence denotes 5.
T142 17171-17319 Sentence denotes There has been a concern regarding the safety of ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) during the ongoing COVID-19 pandemic.
T143 17320-17416 Sentence denotes These agents upregulate expression of ACE2 in various tissues, including on cardiomyocytes [17].
T144 17417-17641 Sentence denotes Since SARS-CoV-2 binds to ACE2 to gain entry into human cells, there is a potentially increased risk of developing COVID-19 or developing more severe disease in patients who are already on background treatment with ACEi/ARB.
T145 17642-17732 Sentence denotes However, to date, no experimental or clinical data have emerged to support these concerns.
T146 17733-17809 Sentence denotes At the same time, the risks of discontinuing these therapies are well known.
T147 17810-17988 Sentence denotes Therefore, several leading professional societies have strongly urged to not discontinue clinically-indicated ACEi/ARB therapy in the event the patient develops COVID-19 [18,19].
T148 17989-17991 Sentence denotes 6.
T149 17992-18149 Sentence denotes Clinicians caring for these patients also need to be fully aware of the potential CV side-effects of various therapies used for treating the viral infection.
T150 18150-18311 Sentence denotes Additionally, various anti-retroviral drugs have significant interactions with cardiac drugs, which need to be considered and appropriate dose modification done.
T151 18312-18463 Sentence denotes More recently, chloroquine/hydroxychloroquine and azathioprine have been proposed as potential therapeutic options, based on preliminary evidence [20].
T152 18464-18578 Sentence denotes Both these drugs are known to prolong QT interval and due caution must be exercised when prescribing these agents.
T153 18579-18861 Sentence denotes Their combination is best avoided and even when using chloroquine/hydroxychloroquine alone, daily electrocardiogram for monitoring QT interval is warranted, esp. in patients with hepatic or renal dysfunction and in those receiving another drug with potential to prolong QT interval.
T154 18863-18895 Sentence denotes 3 Summary and future directions
T155 18896-19173 Sentence denotes Although respiratory illness is the dominant clinical manifestation of COVID-19, the shear burden of the illness implies that a large number of patients with COVID-19 would present with pre-existing CVD or develop new-onset cardiac dysfunction during the course of the illness.
T156 19174-19285 Sentence denotes Considering this, the current understanding about the interplay between CVD and COVID-19 is grossly inadequate.
T157 19286-19486 Sentence denotes It is therefore highly desirable that the future studies on COVID-19 specifically describe the incidence, mechanisms, clinical presentation and outcomes of various CV manifestations in these patients.
T158 19487-19612 Sentence denotes The diagnostic and therapeutic challenges posed by the concurrence of these two illnesses also need to be adequately studied.