Cardiac menefestation of covid 19

1. Cardiac
Manifestation
of COVID-19
DR MD SEEBAT MASRUR
IMO(CARDIOLOGY)
TMC & RCH

3. Cardiovascular disease is a common comorbidity
▪ Cardiovascular disease is a common comorbidity
observed in patients infected with SARS or MERS(with a
prevalence of 10% and 30% respectively).
▪ In hospitalized patients with COVID-19, the prevelence of
any comorbidity was 32% and the most common
underlying disease were
diabetes(20%),hypertension(15%) and other CVDs (15%).
▪ Importantly, the prevalence of these preexisting
conditions was higher in critically ill patients.

4. CVS Involvement in COVID-19
▪ Although the predominant clinical manifestation of
COVID-19 is viral pneumonia, it can also cause
cardiovascular disorders such as myocardial injury,
arrhythmias, ACS and thromboembolism.
▪ Some patients who present without the typical
symptoms of fever or cough may have cardiac symptoms
as the first clinical manifestation of COVID-19.
▪ Myocardial injury throughout the course of COVID-19 is
independently associated with high mortality.

5. Pathophysiology
Ref:https://www.bmj.com/content/371/b
mj.m3862

6. Pathophysiology
Ref:https://www.ahajournals.org/doi/10.1161/JAHA.120.016219

7. SARS-CoV-2 interactions with the RAAS
RAAS participates in the principal homeostatic mechanism
such as regulation of vascular tone , circulatory volume,
organ perfusion , blood clotting , cardiomyocyte growth and
collagen matrix turnover.
The critical balance between the ACE / Ang-II/ AT1R and the
opposing ACE2/ Ang (1-7) / MASR axes is central in (among
others ) the physiological regulation of cardiovascular , BP ,
neural and kidney functions .
SARS –CoV-2 disrupts the fragile balance between the
protective and deleterious RAAS pathways .

8. Pathophysiology of COVID19
▪ SARS-CoV-2 infects human cells by binding to the cell surface protein
ACE2 through the Receptor Binding Domain (RBD) of its spike (S)
protein.
▪ ACE2 is highly expressed in the lungs , heart , vasculature , bowels and
kidney.
▪ In addition to ACE2 , the cellular transmembrane serine protease 2
(TMPRSS2) is required for the priming of the virus S protein.
REF:J Biomed Sci 2021:28:9

9. Phases
▪ Phase 1:Rapid virus propagation due to ACE2, TMPSSR2 genes in
tissues of the respiratory, CVS and GI tracts.
▪ Phase 2: Host-specific uncontrolled inflammatory immune
responses which drive aggressive inflammation, hyper-
cytokinemia, and collateral tissue damage and systemic failure
because of imbalanced ACE/Ang-II/AT1R and ACE2/Ang(1-
7)/MASR axes signaling.
REF: J Biomed SCI.2021:28:9

10. Cardiovascular effects are caused by-
Ref: Am J MED Sci 2021;361(1):14-22
▪ Direct damage may be mediated
through downregulation of ACE2,
vascular endothelial cell
dysfunction, microvascular
dysfunction, pericyte injury and
hypoxemia resulting in Myocarditis,
HF, arrhythmia.
▪ Indirect damage may be mediated
through the release of cytokines(IL-
6), coagulopathy and insulin
resistance resulting in
Thromboembolism & metabolic
disorder.

11. CVS Complications ref:cardiovascular Drugs & Therapy. 2021;35:249-259

12. Interaction
between CVD &
Covid-19
Ref:
https://www.nature.com/articles/s41569-
020-0413-9

13. Possible mechanisms
and cardiovascular
manifestations
Ref:https://heart.bmj.com/content/106/1
5/1132

14. Diagnostic Evaluation
for COVID-19 related
Myocardial Injury
Ref:https://www.onlinejcf.com/article/S1071-
9164(20)30357-2/fulltext
Upto 20-30% of patients hospitalized with
COVID-19 have evidence involvement
manifested by elevated troponin levels,
which associated with worse outcome

15. Interpreting Myocardial Injury

16. Myocardial Injury & myocardial Infarction
Myocardial Injury- There is evidence cTn
values with at least one value above the 99th
percentile URL.
The myocardial injury in considered acute if
there is a rise and/or fall cTn values.
Acute Myocardial infarction-When there is
acute myocardial injury with clinical
evidence of acute myocardial ischemia and
with detection of a rise and/or fall of cTn
values with at least values above 99th
percentile URL.

17. Cardiovascular manifestations in COVID-19
Elevation of cardiac biomarkers
The main findings of this study are that
(i) Nearly one in three patients with a
hospital encounter related to COVID-19
had myocardial injury at the time of
diagnosis, and 21.5% of those presented
with chronic troponin elevation.
(ii) Both chronic and acute myocardial injury
are strongly associated with impaired
survival at 6 months, with an effect that
persists even beyond 30 days after the
infection; and
(iii) The risk of death is similar in patients
presenting with acute compared with
chronic myocardial injury, except for
patients < 65 yrs of age or without CAD.

18. Types of
myocardial injury
To evaluate the acute and chronic
patterns of myocardial injury
among patients with coronavirus
disease-2019
Study with cardiovascular
magnetic resonance, the most
prevalent pattern of myocardial
injury was myocarditis-like (27%),
followed by ischaemia-like (22%),
with no evidence of diffuse
oedema or fibrosis during the
convalescent phase after severe
COVID-19.

19. Ischemic and Non-
Ischemic myocardial
injury

20. Ischemic myocardial injury
Myocardial infarction
▪ Both Type 1 & 2 can occur. Type
2 being more common.
Myocardial injury with DIC
▪ DIC is a life-threatening condition
present in 71.4% (15/21) of non-
survivors with COVID-19.

21. Non-ischemic myocardial injury
Myocarditis and stress-induced cardiomyopathy
▪ Acute and fulminant myocarditis and stress-induced
cardiomyopathy can occur.
▪ The incidence of acute heart failure was 33% (7/21) in critically ill
patients with COVID-19 without a past history of LV systolic
dysfunction.

22. Non-ischemic myocardial injury
Myocardial injury with cytokine release syndrome
▪ Cytokine release syndrome (aka ‘cytokine storm’)
▪ hyperinduction of proinflammatory cytokines such as interleukin
(IL)-1, IL-6, T helper 1 cytokine interferon-gamma, and tumour
necrosis factor-alpha (TNF-α)
▪ It is postulated that proinflammatory cytokines depress myocardial
function immediately through activation of the neural
sphingomyelinase pathway and subacutely (hours to days) via
nitric oxide-mediated blunting of beta-adrenergic signalling.

23. Arrhythmia
Arrhythmia could be the first presentation of COVID-19
A study of 137 patients in Wuhan showed that 7.3% had
experienced palpitations as one of their presenting symptoms for
COVID-19

24. Venous thromboembolism
Due to
▪ Prolonged immobilization
▪ Hypercoagulable status
▪ Active inflammation
▪ Propensity for DIC-patients with COVID-19 are at increased risk of
VTE. The prevalence of ultrasound confirmed deep venous
thrombosis in patients with COVID-19 is 22.7% and 27% in ICU
patients.

25. Treatment /
Management

26. Treatment of Myocarditis
▪ The treatment of Covid-19 related myocarditis
mostly supportive.
▪ Antiviral therapy and immunomodulators can be
of help.
▪ The treatment new-onset HF with a balanced use
of vasopressors, inotropes, diuretics, vasodilators
and fluid therapy may be life-saving.

27. Acute Coronary Syndrome
▪ There is no universally agreed treatment protocol for acute MI in
Covid-19 patients.
▪ In patients with STEMI fibrinolysis may be considered in those with
Low risk STEMI(defined by INF STEMI with no RV involvement or
lateral AMI without hemodynamic compromise).
▪ PCI is more commonly performed at most institutions and remains
the treatment of choice.
▪ Reperfusion therapy with thrombolytics is an attractive option in
stable patients without contraindications. Tenecteplase, the most
fibrin specific agent, is prudent choice in patients with Covid-19.

28. Cardiac Arrhythmias and Sudden Cardiac Arrest
▪ Malignant arrhythmias was noted in 16.7% of patients
hospitalized with Covid-19 and contributed to 44% of
those transferred to ICU.
▪ Is due to myocardial injury and subsequent cardiac
dysfunction.
▪ Drugs causing LQTS such Azithromycin, HCQ etc should
be used with caution.

29. Heart Failure in Covid-19
▪ HF can happen due to myocardial injury and chronic
stable HF is liable to worsen during Covid-19 infection.
▪ HF in patients with Covid-19 can range from mild HFpEF
in the early stages of the illness to severe end-stage HF
and Cardiogenic Shock with high rates of mortality.
▪ Acute HF can be primary presenting manifestation of
Covid-19 infection(HF in 23% and Cardiomyopathy in
33%)

30. Pharmacotherapy

31. Antiplatelets
▪ In a retrospective study, the use of low-dose Aspirin in
patients hospitalized with COVID-19 was associated with
better outcomes.
▪ P2Y12 inhibitor of choice is clopidogrel, although
ticagrelor can also be considered.
▪ Drug-drug and Drug-disease interactions should be kept
in mind

32. Anticoagulant therapy
Due to the high rate of associated arterial thromboembolism and VTE,
prophylactic anticoagulation is essential in the management of
hospitalized patients with COVID-19, although the optimal
thromboprophylaxis regimen is unclear. In a retrospective study of 449
patients with severe COVID-19, 99 patients received unfractionated
heparin or low molecular weight heparin for at least 7 days. No
difference in overall 28-day mortality was observed, but in subgroups of
patients with sepsis-induced coagulopathy score ≥4, or D-dimer >sixfold
of upper limit of normal, the heparin group had lower mortality
compared with the no-heparin group respectively. Another concern
regarding thromboprophylaxis is the drug-drug interaction between
some antivirals.

33. Prophylaxis against VTE
▪ Markedly elevated levels of D-dimer with normal
fibrinogen levels are the hallmark of laboratory finding of
severe Covid-19 associated coagulopathy.
▪ Prophylaxis against VTE is paramount for all hospitalized
patients with more aggressive prophylaxis and screeing
recommended for patients with D-dimer levels above 3.0
ug/ml
Ref Cleveland J Med 2020;87(8):462=468

34. Prevention and treatment Covid-19 associated
Coagulopathy Ref Cleveland J Med 2020;87(8):462=468

35. ACE inhibitors (ACEI)/ Angiotensin Receptor
Blockers (ARB)
▪ Early in 2020, a controversy grew regarding the safe usage of these
drugs in COVID-19 patients. The current consensus agrees to the
continued use of these medications. BRACE CORONA trial was
presented in ESC Congress 2020, which found no significant
difference in the number of days alive and out of hospital through 30
days among subjects receiving continuous ACEI/ARB and hospitalized
for COVID-19 compared to those in whom these medicines were
temporarily suspended. Five common classes of antihypertensive
medications are safe in patients of COVID-19 and do not increase the
likelihood of infection.
▪ At present there are three major studies on ACEi and ARBs in patients
with Covid-19 and they have all reported no harm in use.

36. Beta Blockers
▪ Selective ones are more preferred over nonselective ones.

37. Statins
▪ Statins have beneficial vascular and myocardial effects that are
attributed to their anti-inflammatory effects
▪ Irrespective of Covid-19, a high intensity statins should be
administered to every patient with ACS.
▪ It is advisable to monitor the liver function and creatinine kinase
levels at baseline and periodically thereafter.

38. Remdesivir
▪ The US Food and Drug Administration (FDA) has issued an
emergency use authorization for remdesivir in all patients hospitalized
with COVID-19. Thus far, no prominent cardiovascular side effects
have been reported with Remdesivir, although these may become
apparent with future use during the COVID-19 pandemic

39. Hydroxychloroquine and Chloroquine
▪ Large medical center in New York City found no apparent benefit from
hydroxychloroquine. The use of hydroxychloroquine alone or
hydroxychloroquine plus azithromycin did not improve a composite
endpoint of intubation or death.
▪ Chloroquine has been noted to cause atrioventricular blocks and
prolonged QTc, especially when combined with azithromycin.

40. Azithromycin
▪ Azithromycin was commonly used in combination with
hydroxychloroquine as a treatment early in the pandemic. However,
several studies of this combination have not shown any clinical benefit.

41. Lopinavir-ritonavir
▪ Lopinavir and ritonavir are protease inhibitors approved by the FDA
for HIV-1 infection. In a recent study published in the New England
Journal of Medicine, researchers observed no survival benefit after
treatment with lopinavir-ritonavir in hospitalized adults with severe
COVID-19

42. Steroids
▪ The World Health Organization has recommended using systemic
steroids to treat COVID-19 infection.Corticosteroids are known to
possess potent anti-inflammatory effects, and they have been studied
extensively in the treatment of sepsis and ARDS. However, they are
also known to cause fluid retention, electrolyte derangement,
hyperglycemia, and hypertension. At the onset of the COVID-19
pandemic, concerns about potential harm from steroids in COVID-19
were based on data collected and extrapolated during the previous
SARS-CoV outbreak. Nonetheless, the recent RECOVERY trial
compared dexamethasone 6 mg once daily for up to 10 days versus
usual care alone in hospitalized patients with COVID-19 receiving
invasive mechanical ventilation or oxygen. Dexamethasone reduced
28-day mortality by one-third in patients on a mechanical ventilator
and by one-fifth in patients requiring oxygen therapy.

43. Tocilizumab
▪ Tocilizumab, an anti–IL-6 receptor antibody, has been investigated to
treat hospitalized COVID-19 patients. IL-6 levels are elevated in
COVID-19 patients and significantly elevated in patients with severe
disease. Tocilizumab’s potential efficacy lies in its ability to reduce the
inflammatory response, including the cytokine storm that contributes to
ARDS and death. As for cardiac side effects, tocilizumab is known to
increase cholesterol levels, but there are conflicting reports on its effect
on long-term cardiac morbidity and mortality.

44. Convalescent Plasma
▪ Convalescent plasma for the treatment of COVID-19 patients is
obtained from individuals who have recovered from COVID-19 and
have generated an immune response. Small randomized trials and case
studies have shown some benefit from convalescent plasma in
hospitalized patients with severe COVID-19, especially if given early
in the disease course. The FDA has granted emergency use
authorization for convalescent plasma in hospitalized patients with
COVID-19.

45. Ivermectin
▪ The FDA has issued a warning
against using Ivermectin to prevent
or treat COVID-19 infection.
▪ In an earlier version of this story,
David Boulware incorrectly cited an
amount and concentration of
animal ivermectin available online
and calculated that it would be 100
times the normal human dosage,
leading to toxicity. Ivermectin, at
the amounts and concentration
typically available online, would be
more than seven times the normal
dosage for an adult human, which
could still lead to toxicity.

46. Long Term Effects

47. NICE-Covid-19 Recovery
▪Acute Covid-19(Within 4 weeks after
diagnosis)
▪Ongoing Covid-19(4 to 12 weeks after
diagnosis)
▪Long Covid-19(Over 12 weeks after
diagnosis)

48. Prolonged Symptoms

49. Cardiopulmonary
Symptoms
Shortness of Breath
Cough
Chest Pain

50. Cardiovascular System
▪ Hypertension was the most
common cardiac comorbidity.
▪ The majority of patients had
elevated troponin.
▪ Histologic examination showed
myocyte hypertrophy and
remote myocardial injury as
patchy interstitial fibrosis.
▪ Survey of the coronary tree
showed at least moderate
atherosclerosis.
▪ Acute myocardial ischemia was
observed.
▪ Myocarditis were rare.

51. THANK
YOU
World Heart Day 2021 theme

52. What is the ACE2 receptor?
▪ ACE2 is a protein on the surface of many cell types. It is an
enzyme that generates small proteins – by cutting up the larger
protein angiotensinogen – that then go on to regulate functions
in the cell.
▪ Using the spike-like protein on its surface, the SARS-CoV-2
virus binds to ACE2 – like a key being inserted into a lock – prior
to entry and infection of cells. Hence, ACE2 acts as a cellular
doorway – a receptor – for the virus that causes COVID-19.

53. Where in the body is it found?
▪ ACE2 is present in many cell types and tissues including the
lungs, heart, blood vessels, kidneys, liver and gastrointestinal
tract. It is present in epithelial cells, which line certain tissues
and create protective barriers.
▪ The exchange of oxygen and carbon dioxide between the lungs
and blood vessels occurs across this epithelial lining in the lung.
ACE2 is present in epithelium in the nose, mouth and lungs. In
the lungs, ACE2 is highly abundant on type 2 pneumocytes, an
important cell type present in chambers within the lung called
alveoli, where oxygen is absorbed and waste carbon dioxide is
released.

54. Does everyone have the same number of ACE2 on
their cells?
▪ No. ACE2 is present in all people but the quantity can vary
among individuals and in different tissues and cells. Some
evidence suggests that ACE2 may be higher in patients with
hypertension, diabetes and coronary heart disease. Studies
have found that a lack of ACE2 (in mice) is associated with
severe tissue injury in the heart, lungs and other tissue types.

55. Which organs are most severely damaged by
SARS-CoV-2?
▪ The lungs are the primary site of injury by SARS-CoV-2 infection,
which causes COVID-19. The virus reaches the lungs after entry in
the nose or mouth.
▪ ANG II drives lung injury. If there is a decrease in ACE2 activity
(because the virus is binding to it), then ACE2 can’t break down the
ANG II protein, which means there is more of it to cause inflammation
and damage in the body.
▪ The virus also impacts other tissues that express ACE2, including the
heart, where damage and inflammation (myocarditis) can occur. The
kidneys, liver and digestive tract can also be injured. Blood vessels
may also be a site for damage.
▪ In a recent research paper, we argued that a key factor that
determines severity of damage in patients with COVID-19 is
abnormally high ANG II activity.