|Year : 2020 | Volume
| Issue : 2 | Page : 40-44
Covid cardiology: A neologism for an evolving subspecialty
Satyanarayana Upadhyayula MD, FEM, FIMSA, MIAE 1, Ravi R Kasliwal MD, DM, FIMSA, MNAMS, FASE 2
1 Division of Cardiology, Medanta Mediclinic, Defence Colony, New Delhi, India
2 Division of Clinical and Preventive Cardiology, Gurgaon, Haryana, India
|Date of Submission||30-May-2020|
|Date of Acceptance||09-Jun-2020|
|Date of Web Publication||01-Aug-2020|
Dr. Ravi R Kasliwal
Division of Clinical and Preventive Cardiology, Medanta Heart Institute, Room No. 9, 3rd Floor, Medanta - The Medicit, Sector 38, Gurgaon - 122 001, Haryana
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Upadhyayula S, Kasliwal RR. Covid cardiology: A neologism for an evolving subspecialty. J Clin Prev Cardiol 2020;9:40-4
The word “Corona” literally means crown or the halo around the sun. The World Health Organization (WHO) has named the coronavirus disease as COVID-19 and the virus that causes it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is an enveloped, nonsegmented single-stranded, positive-sense ribonucleic acid (RNA) virus with a genome 96.2% identical to a bat coronavirus.
“It is a genius of a virus, arguably with a firmament of intelligence somewhere in its short genome, for when a drug or vaccine is about to be declared, it mutates in a jiff.”
While cardiovascular diseases (CVD) are undoubtedly ubiquitous among the noncommunicable diseases, COVID 19 has earned its corresponding place among the communicable diseases in just a few months (First case reported on November 17, 2019 in Wuhan, China and within 116 days was declared a pandemic by the WHO on March 11, 2020). When two ubiquitous diseases (CVD and COVID 19) unleash their fury in a streamlined fashion it would be sagacious to deal with the resulting super malady as a separate subspecialty – COVID CARDIOLOGY-a portmanteau word for COVID 19 resulting in CVD or CVD with superadded COVID 19 infection [Figure 1].
|Figure 1: Wenn diagram showing COVID 19 overlapping cardiovascular diseases. The overlap area is the COVID CARDIOLOGY|
Click here to view
Salient features in favor of the neologism “COVID CARDIOLOGY” are as follows:
- COVID 19 arrived with a big bang in Wuhan and spread globally at blitzkrieg speed to become a pandemic
- It mutates fast and is going to stay
- By the time effective drugs/vaccines arrive for general use in the market, newer strains would already have taken deep-rooted positions in the general population
- In the best-case scenario, we may be able to control and contain SARS-CoV-2 but not eradicate in
- We have seen only the short-term effects of SARS-CoV-2 on the cardiovascular (CV) system, and the long-term manifestations are yet to be realized
- It is the greatest pandemic of modern times and has been declared a Public health Emergency of international concern by the WHO
- It not only affects the CV system but also the drugs used to treat it interact with many drugs used in Cardiology
- Hence, there is an unmet need for guidelines regarding the management of COVID 19 in Pregnancy, Fetal, Neonatal, Pediatric, Adult, and Geriatric patient cohorts with and without preexisting CVD
- It has drilled an economic hole in the global gross domestic product upwards of 8.4 trillion USD-highest ever in the known history of humankind. It has not only made its indelible mark but also made its presence felt
- Eradicating COVID 19 would be an unprecedented gargantuan task. Even if we are able to conquer COVID 19, a fast mutating virus, can COVID 20 be far behind? Both entities “COVID 19” and “CARDIOLOGY” are here to stay and hence the neologism “COVID CARDIOLOGY” [Figure 1].
SARS-CoV-2 entry into cells is facilitated by receptor-mediated endocytosis via angiotensin-converting enzyme 2, a type I integral membrane protein that is highly expressed in lungs alveolar cells. The COVID 19 symptoms include fever, sore throat, nausea, conjunctivitis, headache, myalgias, fatigue, diarrhea, lymphopenia, dry cough, tiredness, joint aches and pains, loss of taste (ageusia), loss of speech (aphasia), loss of smell (anosmia), skin rashes, discoloration of fingers/toes, shortness of breath, chest pain/or pressure, loss of movement (paralysis), pneumonia, adult respiratory distress syndrome, acute myocardial injury, myocarditis, acute coronary syndromes, arrhythmias, venous thromboembolism, distributive/cardiogenic shock. Children with fever, multiple inflamed organs requiring hospitalization, a confirmed active or recent COVID 19 infection – formerly referred to as pediatric multisystem inflammatory syndrome (MIS) similar to Kawasaki disease – has now been renamed as MIS in children by Centers for Disease Control and Prevention.
Patients with preexisting CVD appear to have worse outcomes with superadded COVID-19 infection. CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care. In addition, repurposed drug therapies under investigation for COVID-19 (dexamethasone, tocilizumab, ivermectin, doxycycline, azithromycin, remdesivir, favipiravir, umifenovir, lopinavir, ritonavir, ribavarin, interferon beta-1b, oseltamivir, darunavir, arbidol) may have significant drug-drug interactions with CV medications.
The prevalence of CVD-hypertension (17.1%), cardiac and cerebrovascular disease (16.4%), and diabetes (9.7%) – in COVID 19 has been substantial according to a meta-analysis of 6 studies (n = 1527). Increased case-fatality rates were observed in CVD (10.5%), diabetes (7.3%), and hypertension (6.0%) in confirmed COVID-19 cases from Wuhan, China (n = 44,672).
In a meta-analysis of four studies (n = 341), cardiac troponin I levels were significantly higher in those with severe COVID-19-related illness compared with in those with nonsevere disease (25.6; 95% confidence interval [CI]: 6.8–44.5). Furthermore, myocardial injury occurs in 7%–17% of hospitalized patients with the disease and is significantly more common in patients admitted to the intensive care unit (ICU) versus non-ICU (22.2% vs. 2.0%; P < 0.001) and among those who died versus survivors (59% vs. 1%; P < 0.0001).,,,,,,
Other CV manifestations include palpitations (7.3%) cardiac arrhythmia (16.7% in ICU patients vs. 6.9% in non-ICU patients), cardiomyopathy and heart failure (23%) substantial delays in door-to-device time in STEMI, thrombosis (31%) as well as elevated D-dimer levels (>1 g/l were strongly associated with in-hospital deaths. odds ratio: 18.4; 95% CI: 2.6–128.6; P = 0.003)., 8, ,,, Interestingly, inflammation (both vascular and endothelial) and immune dysfunction seem to be an important underlying common factor in the etiopathogenesis of COVID 19 as well as CVD.
Mild disease turning to severe form is initiated by immune dysfunction and cytokine dysregulation resulting in what is called as “cytokine storm syndrome” (CSS) an inflammatory cytokine profile which is similar to secondary hemophagocytic lymphohistiocytosis (sHLH) an under-recognized, infection catalyzed, hyperinflammatory syndrome characterized by a fulminant and fatal hypercytokinemia with multiorgan failure. SARS-CoV-2 elicits an intense local or systemic immune response (hyperinflammation) in the lung, myocardium, etc., leading to multiorgan organ failure with high morbidity and mortality. It is characterized by increased interleukin (IL)-2, IL-7, granulocyte colony-stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumor necrosis factor-α. All patients with suspected severe CSS or sHLH should be screened for hyper inflammation using laboratory trends (e.g., increasing ferritin, decreasing platelet counts, or erythrocyte sedimentation rate) and the H Score to identify the subgroup of patients for whom immunosuppression could improve mortality. Therapeutic options include steroids, intravenous immunoglobulin, selective cytokine blockade (e.g., anakinra or tocilizumab), and Janus Kinase inhibition.
Therapeutic measures being evaluated include repurposed drug (antiviral, antibacterial, antiprotozoal), plasma therapy, vaccines (DNA, RNA, Live Attenuated, Protein Sub Unit, Viral Vector), etc., For instance, chloroquine an anti-malarial drug blocks virus infection by increasing the endosomal pH required for virus/cell fusion and has inhibitory activity in SARS-CoV-2., Although very effective, clinical usage is limited by CV adverse effects. Both Chloroquine, as well as Hydroxychloroquine, cause restrictive or dilated cardiomyopathy/or conduction abnormalities thought to be due to intracellular inhibition of lysosomal enzymes in the myocyte., In addition, chloroquine inhibits CYP2D6 leading to increased concentration of metoprolol, carvedilol, propranolol, or labetalol, which are also metabolized via CYP2D6. Chloroquine, along with electrolyte abnormalities or with concomitant use of QT-interval–prolonging agents may lead to torsade des pointes. In a multinational registry analysis (n = 96,302) decreased in-hospital survival (16·4%; hazards ratio 1·365, 95% CI 1·218–1·531) and an increased frequency of ventricular arrhythmias (4.3%; hazards ratio 3.561, 95% CI 2.760–4.596) were noted. Similarly, methyl prednisolone though very useful in severe COVID 19, especially in reducing mortality, has several adverse effects such as fluid retention, electrolyte derangement, hypertension, and drug interactions with warfarin.
In one study (n = 44,672), Wu et al. showed that health-care workers are at elevated risk (3.8%) for contracting COVID 19. On a risk-mitigating note, in COVID 19 negative patients with no prior CVD use simple universal precautions (handwashing, disinfection, physical distancing), COVID 19 positive patients with no prior CVD close monitoring for COVID 19 complications (myocarditis, heart failure, cardiogenic shock, acute coronary syndrome, venous thrombo-embolism, stress cardiomyopathy, arrhythmias), COVID 19 negative patients with prior CVD use digital methodologies and universal precautions (telemedicine, e-visits, self-monitoring, remote monitoring, prioritizing visits and procedures, personal protective equipment), COVID 19 negative patients with no prior CVD, take preventive measures (heightened awareness of CV sequelae, closer monitoring, CV medication, and toxicities).
When it comes to management, provide high-quality care while minimizing exposure to COVID 19 during CV procedures – interventional, electrophysiology, cardiac surgery-(minimize staffing, optimize medications, reschedule elective procedures, use negative pressure catheterization laboratories/operation theaters, consider fibrinolysis if Percutaneous Coronary Intervention is not possible). Minimize nonessential/nonurgent in-person health-care worker-patient interactions as much as possible and limit and reschedule elective cardiac catheterization, operating room, and echocardiographic procedures. In addition, repurposing cardiac ICUs as medical ICUs for the care of patients with COVID-19 will likely become necessary, but this may limit the quality of specialty care for CV patients.
The sheet anchor of COVID 19 management is the upcoming data from a large number of systematic clinical trials sponsored by private and governmental institutions. Unlike previous epidemics and pandemics caused by viruses/bacteria (Marburg virus, Ersenia Pestis, Ebola virus, Rabies, HIV, Smallpox, Hantavirus, Influenza, Dengue, Rotavirus, Middle East respiratory syndrome) in history - prehistoric epidemic (Circa 3000 B.C), Plague of Athens (430 B.C), Antonine Plague (A.D. 165–180), Plague of Cyprian (A.D. 250–271), Plague of Justinian (A.D. 541–542), The Black Death (1346–1353), Cocoliztli epidemic (1545–1548), American Plagues (16th century), Great Plague of London (1665-1666), Great Plague of Marseille (1720–1723), Russian plague (1770–1772), Philadelphia yellow fever epidemic (1793), Flu pandemic (1889-1890), American polio epidemic (1916), Spanish Flu (1918–1920), Asian Flu (1957–1958), AIDS pandemic and epidemic (1981-present day), H1N1 Swine Flu pandemic (2009–2010), West African Ebola epidemic (2014–2016), Zika Virus epidemic (2015-present day) – COVID 19 has attracted large number of systematic controlled clinical trials worldwide.
At the time of this writing, the total number of registered ongoing/completed COVID-19 clinical trials were 2704 (1114 clinical trials registered with clinicaltrials.gov and 1590 clinical trials registered with WHO's International Clinical Trials Registry Platform database). For comparison, the total number of ongoing/completed CVD trials registered were 64,803 (41,035 clinical trials registered with clinicaltrials.gov and 23,768 clinical trials registered with WHO's International Clinical Trials Registry Platform).
Positive results from ongoing clinical trials indicate that Remdesivir (a broad spectrum re-purposed antiviral drug produced by Gilead Sciences Inc.) and Dexamethasone ( first synthesized in 1957 by Philip Showalter Hench and approved for medical use in 1961; a glucocorticoid agonist well known for its anti-inflammatory / immune-suppressive properties) are of good promise in the treatment of COVID 19. While Remdesivir is useful in the initial moderate stages of Covid 19, Dexamethasone was found to be useful in the later severe stages of the disease.
The RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial is a large, randomized controlled trial in which (n=11,500) patients have been randomized to the following treatment arms:
- Low-dose Dexamethasone
- Convalescent plasma
- No additional treatment
Overall, dexamethasone reduced the risk of 28-day mortality by 17% with a highly significant trend showing greatest benefit among those on ventilators. Dexamethasone reduced deaths by 33% in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; P=0.0003) and by 20% in other patients receiving oxygen only (0.80 [0.67 to 0.96]; P=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75]; P=0.14).
“This is the most important trial result for COVID-19 so far. It shows significant reduction in mortality in those requiring oxygen or ventilation from a widely available, safe and well known drug. We should all be grateful to the patients who volunteered and those who made this trial possible. It will save lives around the world.”- Chris Whitty
Tocilizumab fared well in a retrospective, observational cohort study (n=544) of severe COVID-19 pneumonia patients who were admitted to tertiary care centers in Bologna and Reggio Emilia, Italy. All patients were treated with the standard of care (i.e. supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab (intravenously at 8 mg/kg bodyweight in two infusions). After adjustment for sex, age, recruiting centre, duration of symptoms, and sequential organ failure assessment (SOFA) score, tocilizumab treatment was associated with a reduced risk of invasive mechanical ventilation or death (adjusted hazard ratio 0·61, 95% CI 0·40–0·92; P=0·020).
Tocilizumab also fared well in a small Chinese retrospective, uncontrolled study (n=21) with severe COVID-19 symptoms who received treatment with the IL-6 blocker tocilizumab. Within 24 hours of starting tocilizumab therapy, fevers and elevated C-reactive protein levels resolved, and levels of IL-6 and other proinflammatory cytokines declined. Use of supplemental oxygen dropped in 15 patients, oxygen saturation levels stabilized in all patients, the 2 ventilated patients were weaned, and all patients recovered.
Remdesivir (GS-5734™) a RNA polymerase inhibitor as well as a nucleoside analogue prodrug with inhibitory effects on SARS-CoV-1, SARS-CoV-2. It is authorized for use under an Emergency Use Authorization (EUA) only for the treatment of patients with suspected or laboratory-confirmed SARS-CoV-2 infection and severe COVID-19 (patients with an SpO2 ≤ 94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation).
A recent double-blind, randomized, placebo-controlled trial (n=1963) of intravenous Remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement; randomly assigned to receive either Remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. based effective drugs for therapy of Covid 19. Clinical trials proved that Hydroxychloroquine, Lopinavir-Ritonavir are ineffective against Covid 19.
At the time of this writing Dexamethasone and Remdesivir are the only evidence based effective drugs for therapy of Covid 19.
Similarly, out of the over 155 ongoing vaccine trials, the WHO has recognised 8 as frontrunners for potential COVID 19 vaccine. Recently, Moderna Inc. has announced positive results with its mRNA-1273 vaccine. The mRNA vaccine technology can lead to a paradigm shift in vaccinology and could be the next game-changing vaccine platform. The mRNA vaccines are intrinsically safe, flexible, with the superior immunological response. They produce a balanced immune response comprising both cellular and humoral immunity without major histocompatibility complex (MHC) haplotype restriction.
To sum up, the diagnostic, therapeutic, and academic landscape of cardiology has been endangered and imperiled by COVID 19 by virtue of the sephulcre health risks it poses on patients, clinicians, medical health staff, trainees and their families. COVID 19 the crucible of crisis and its aftermath of prolonged isolation has brought us together through the logical emergence of newer digital virtual technologies such as telehealth, telemedicine, tele-cardiology, tele-echocardiography, mobile health, mobile-based applications, inter-institutional collaborations, virtual grand rounds, webinars etc., which are open to the medical fraternity as well as the general public.
In hindsight, it is all about a spine chilling experience due to the big bang arrival of an unknown disease, caused by an unknown virus-which is perspicuous as most of us were not trained in battlefield medicine. The frightening experience it has evoked melted the hubris in medical, social, and political circles to humility. Medical fraternity probably requires a periodic jab of battlefield medicine training to face similar blitzkrieg pandemics as COVID 19 in future.
Finally, in any society lives and livelihoods go together, both are important, interdependent and inseparable. In a pandemic the motto should be “saving lives without sacrificing livelihoods.”
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