- Patients with cardiovascular disease have a higher mortality rate from COVID-19 according to data from China. - The pathophysiology of cardiac involvement in COVID-19 can include hypoxia, hyperinflammation leading to cardiac dysfunction, direct viral myocarditis, and increased risk of thrombosis. - Treatment is mainly supportive, though renin-angiotensin-aldosterone system inhibitors should generally be continued in stable patients, and immunosuppression or modulation may help in some cases.

1. Covid-19 and Heart : What do we know so far?
Dr Syed Raza , MD,MRCP, FRCP, CCT, FACC, FESC
Consultant Cardiologist
Awali Hospital , Bahrain

2. Objectives
• Overview
• Patho-physiology
• Management strategy
• Key learning points

6. Large-scale epidemiological data from China has identified that patients
with cardiovascular disease have a higher mortality rate from COVID-19
(10.5% vs 0.9% for those without any comorbid conditions, [China CDC,
2020])

8. Cumulative Incidences of Diagnosed Covid-19 and Cases of Out-of-
Hospital Cardiac Arrest (OHCA) in Four Provinces in Lombardy, Italy,
during the 40 days after February 20 in 2019 and 2020.

10. Patho-physiology
• 1. Hypoxia due to lung involvement – cardiac ischemia
• 2. Systemic hyperinflammation
a. alter cardiac pump function – cardiogenic shock
b. rapture of vulnerable atherosclerotic plaque -ACS
c. micro and macrovascular thrombosis – ACS
3. Direct cardiac muscle involvement – myocarditis

11. Myocarditis
Infarction

13. Why young and healthy patients are dying of
COVID-19 ?
• 1. Genetic predisposition
• 2. Poor immunity
• 3. Inherited lung condition,
Asthma
• 4. Smoker
• 5. High viral load
• 1. Acute fulminant myocarditis -
Acute cardiac decompensation &
malignant arrhythmia
• 2. Pro-thrombotic state –
coronary/cerebral/lungs

14. Definition of Myocardial Injury
1.Serum levels of cardiac
biomarkers were above the
99th percentile upper
reference limit
2. New changes on ECG
3. New changes on
Echocardiogram

16. ACE 2

17. ACE inhibitors and angiotensin receptor blockers
in COVID-19
Based on the uncertainty regarding the overall effect of
RAAS inhibitors (ACE inhibitor (ACEI) and angiotensin
receptor blocker (ARB) therapy) in covid-19, multiple
specialty societies ( ACC/AHA/HFSA/ESC ) currently
recommend that RAAS inhibitors be continued in patients
in otherwise stable condition.

18. Hydroxychloroquine/Chloroquine and
Azithromycin in COVID-19
Azithromycin interferes minimally
with the cytochrome P-450
Hydroxychloroquine /Chloroquine
is metabolized by CYP2C8 and
CYP3A4/5
Enhanced risk of significant QT
prolongation /Torsade Pointe
(polymorphic VT)

20. Cardiac management
1. Supportive treatment with anticoagulation,
2. Continued use of renin-angiotensin-aldosterone
system inhibitors.
3. Arrhythmia monitoring,
4. Immunosuppression or modulation
5. Mechanical circulatory support – ECMO / IABP

23. Catheterization Laboratory in the COVID Era

25. Key Learning Points
• Cardiovascular system is involved in a small proportion of patients.
• CV involvement does lead to increase the mortality.
• Often a cause for sudden death
• Complex patho-physiology
• Treatment is mainly supportive
• Definitive treatment is experimental.
• COVID-19 has had a significant impact on usual Cardiology practice.

28. • angiotensin receptor blockers (ARBs) and an ACE inhibitor (ACEI) upregulated
ACE2 expression in animal studies,
• here is no clinical or experimental evidence supporting that ARBs and ACEIs
either augment the susceptibility to SARS-CoV-2 or aggravate the severity and
outcomes of COVID-19 at presen
• ACE2 degrades angiotensin II to generate angiotensin 1-7, which activates the
mas oncogene receptor that negatively regulates a variety of angiotensin II
actions mediated by angiotensin II type 1 receptor (AT1R) [26]. Therefore, it is
thought that the ACE2/angiotensin 1-7/mas receptor axis has counteracting
effects against the excessively activated ACE/angiotensin II/AT1R axis, as seen in
hypertension, cardiac hypertrophy, heart failure, and other CVD
• Ang-(1–7) as a vasodilator and anti-trophic peptide in cardiovascular drug therapy

40. • Among 138 patients hospitalized with COVID-19 in Wuhan, acute
cardiac injury was diagnosed in
• 7% patients
• 16.7 % patients were noted to have cardiac arrhythmias .
• COVID-19 involvement in the heart has ranged from asymptomatic
myocardial injury to acute coronary syndrome, mild to fulminant
myocarditis, stress cardiomyopathy and cardiogenic shock
• Furthermore, underlying cardiovascular disease or risk factors and
myocardial injury have been shown to portend poor prognosis in
these patients

41. MYOCARDITIS
• Limited clinical experience indicates that SARS-CoV-2 may lead to fulminant myocarditis;
• • Myocarditis should be suspected in patients with COVID-19 and acute-onset chest pain, ST
segment changes, cardiac arrhythmia and haemodynamic instability. In Last updated on 21 April
2020. © The European Society of Cardiology 2020. All rights reserved Page | 58 addition, LV
dilatation, global/multi-segmental LV hypocontractility (on POC echocardiography), and significant
increase in cardiac troponin and BNP/NTproBNP levels, without significant CAD could also be
present;
• • Suspicion of myocarditis should be raised in COVID-19 patients with acute HF/CS without pre
existing CV disorder;
• • CCTA should be the preferred approach to rule out concomitant CAD;
• • CMR (if available) may be used for further diagnostic assessment;
• • Endomyocardial biopsy is not recommended in COVID-19 patients with suspected myocarditis;
• • No clear recommendation can be given for SARS-CoV-2-associated myocarditis treatment.

42. Heart may be affected, and this can occur in individuals with or
without a prior cardiovascular diagnosis. Evidence of myocardial injury,
as defined as an elevated troponin level, is common among patients
hospitalized with COVID-19, with putative causes including stress
cardiomyopathy, hypoxic injury, ischemic injury (caused by cardiac
microvascular damage or epicardial coronary artery disease), and
systemic inflammatory response syndrome (cytokine storm). A minority
of patients with an elevated troponin level present with symptoms and
signs suggestive of an acute coronary syndrome

43. • Patients with cardiovascular disease, hypertension, obesity, and diabetes are at
increased risk of a poor prognosis.
• Patients infected with the virus SARS-CoV-2 and its clinical disease COVID-19 are
often minimally symptomatic or asymptomatic. More severe presentations
include pneumonia and acute respiratory distress syndrome.
• In some patients, the heart may be affected, and this can occur in individuals with
or without a prior cardiovascular diagnosis. Evidence of myocardial injury, as
defined as an elevated troponin level, is common among patients hospitalized
with COVID-19, with putative causes including stress cardiomyopathy, hypoxic
injury, ischemic injury (caused by cardiac microvascular damage or epicardial
coronary artery disease), and systemic inflammatory response syndrome
(cytokine storm). A minority of patients with an elevated troponin level present
with symptoms and signs suggestive of an acute coronary syndrome.

51. • Patients with pre-existing CVD appear to have worse outcomes with COVID-19.
• • CV complications include biomarker elevations, myocarditis, heart failure, and venous
thromboembolism, which may be exacerbated by delays in care.
• • Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV
medications.
• • Health care workers and health systems should take measures to ensure safety while providing
high-quality care for COVID-19 patients.

56. • According to available clinical data, ≈15% to 30% of the COVID‐19 patients are with hypertension
and ≈2.5% to 15% are with coronary heart disease.3, 4, 5 Angiotensin‐converting enzyme inhibitors
(ACEIs)/angiotensin receptor blockers (ARBs) are widely used in the treatment of these
cardiovascular diseases. Interestingly, several studies have shown that ACEIs/ARBs exhibit ability
to upregulate ACE2 expression in addition to their main pharmacological effect to inhibit
angiotensin‐converting enzyme 1 (ACE1) or block angiotensin II type 1 receptor.6, 7, 8 Considering
that ACE2 expression might correlate with the susceptibility to SARS‐CoV‐2, intake of ACEIs/ARBs
might predispose patients to the infection of SARS‐CoV‐2. Therefore, some cardiologists
suggested that patients should discontinue ACEIs/ARBs to avoid the potential increased risk of
SARS‐CoV‐2 infection.9
• However, there is evidence demonstrating that the activation of the renin‐angiotensin system
(RAS) and the downregulation of ACE2 expression are involved in the pathological process of lung
injury after SARS‐CoV infection.10 Recently, it has been reported that serum level of angiotensin II
is significantly elevated in COVID‐19 patients and exhibits a linear positive correlation to viral load
and lung injury.11 Activation of the RAS can cause widespread endothelial dysfunction and varying
degrees of multiple organ (heart, kidney, and lung) injuries. Thus, intake of ACEIs/ARBs might
probably relieve the lung injury and absolutely decrease heart and renal damage resulting from
the RAS activat

57. Potential Heart Injury in COVID‐19
• As with SARS, patients with COVID‐19 also showed potential cardiac injuries. Chen et al reported that among
the 99 confirmed COVID‐19 patients admitted to Wuhan Jinyintan Hospital, 13 (13%) presented elevated
creatine kinase and 75 (76%) showed the elevation of lactate dehydrogenase.3 Wang et al described the
clinical characteristics of 138 hospitalized COVID‐19 patients at Zhongnan Hospital of Wuhan University and
found elevated hypersensitive troponin I in 10 (7.2%), whereas 23 (16.7%) had arrhythmia.4 Besides, Guan
et al extracted the data on 1099 COVID‐19 patients from 552 hospitals in 31 provinces/provincial
municipalities and found that 90 of 675 (13.7%) were with an elevated creatinine kinase level and 277 of 675
(37.2%) showed an increased lactate dehydrogenase level.5 The myocardial dysfunction can be indirect,
caused by reduced oxygen supply, severe lung failure, and the cytokine storm after the SARS‐CoV‐2 infection.
However, there is also the possibility that it might be attributable to the decreased activity of ACE2 in the
heart, just like SARS. Oudit et al18 detected the presence of SARS‐CoV and a marked decreased ACE2
expression in the heart of intranasal SARS‐CoV–infected mice. They also reported that SARS‐CoV was isolated
from 7 of 20 of the human autopsy hearts, and the myocardial damage was accompanied by the decreased
protein expression of myocardial ACE2 as well. Recently, an autopsy case of COVID‐19 was reported in
Chinese.19 Liu et al19 observed a moderate amount of transparent light‐yellow liquid in the pericardial cavity
and mild epicardial edema in an 85‐year‐old man who died from COVID‐19. They also reported that the
myocardial section was gray‐red fish‐like. Considering that this old patient showed a history of coronary
heart disease, whether the myocardial injury was associated with SARS‐CoV‐2 infection is still unclear.
However, direct evidence demonstrating that SARS‐CoV‐2 infects the heart and decreases the ACE2
expression is currently lacking.

58. Influence of cardiovascular and other comorbidities on CFR from respiratory viral infections.
Yu Kang et al. Heart doi:10.1136/heartjnl-2020-317056
Copyright © BMJ Publishing Group Ltd & British Cardiovascular Society. All rights reserved.

60. • ole. Based on epidemiological data, palpitations are present in 7.3% of patients,
and a significantly higher proportion of critically ill patients develop arrhythmias,
although these have not yet been characterized.15,49 Arrhythmias in this patient
population can arise secondary to hypoxemia, metabolic derangements, systemic
inflammation, or myocarditis.
• acute coronary syndromes and acute myocardial infarction (AMI) can occur in
patients with COVID-19, but the incidence of such events is unclear. In principle,
risk for acute coronary syndromes in afflicted patients may be increased due to
heightened thrombotic proclivity, as evidenced by significantly elevated D-dimer
levels.15–17 Underlying this risk are known predisposing factors related to
inflammation: endothelial and smooth muscle cell activation; macrophage
activation, and tissue factor expression in atheromatous plaque; and platelet
activation with further elaboration of inflammatory mediators.50