Cardiovascular Diseases in Coronavirus Infection is a great concern and a major factor contributing to mortality.

Among patients with no pre-existing cardiac disease who died of COVID-19, 11.8% had substantial cardiac damage as evidenced by very high troponin levels and cardiac arrest during hospitalization.

The disease has caused 108,837 deaths (as of 12th April 2020) and we are still counting. Various treatment modalities are being tried to save the patients from dying, however, the results are far less fruitful.

The CDC and WHO have identified people who are at risk of dying from Coronavirus. These include [Ref]:

• People aged 65 years and older
• People who are immunocompromised including HIV exposed/infected, immune-deficient people, people on disease-modifying drugs and steroids, those on chemotherapeutic drugs for cancer, and patients who have had an organ transplant.
• People with hypertension and heart diseases especially those with heart failure
• Morbid obese individuals with a body mass index of 40 or more
• People who live in a nursing home or long-term care facility
• Pregnant females.
• People with preexisting chronic lung diseases including those with moderate to severe asthma and smokers
• CO-existing medical conditions such as those with diabetes, renal failure, or liver disease (particularly if the disease is uncontrolled)

We can understand the list is all about those patients who are at risk of dying from any disease, but why hypertensives (and cardiac patients)?

Also, some patients who were later diagnosed with SARS Cov2 infection did not present with fever, cough or shortness of breath, rather they went to their cardiologists with symptoms of palpitations and chest tightness.

One study found that 7.2% of 138 COVID-19 patients experienced acute cardiac damage, 8.7% experienced a shock, and 16.7% experienced cardiac arrhythmias. The majority of these patients needed support for intensive care.

Patients with COVID-19 infection have been found to have prevalence rates of diabetes, hypertension, and cardiac disorders that are, respectively, 17.1%, 16.4%, and 9.7%. [Ref].

How the Coronavirus affects the heart?

The coronaviruses including the SARS CoV-2 (COVID-19) enter the host cells by using the ACE2 receptors present on the cell surfaces in the lungs, heart, and blood vessels.

SARS CoV-2 primarily enters the body via the respiratory system and causes an inflammatory reaction in the lungs. Most patients develop shortness of breath, cough, and fever when they develop SARS CoV-2 associated pneumonia.

The ACE2 receptors are involved in the development of diabetes mellitus and hypertension.

In patients with cardiovascular diseases and hypertension and especially in those patients who are using ACE inhibitors, the ACE2 receptors are up-regulated. When more ACE2 receptors are present, the virus will gain entry into the host cells more easily and in a larger quantity.

On the contrary, studies have found that SARS CoV2 infection is associated with the downregulation of the ACE2 and activation of the RAAS (Renin-angiotensin-aldosterone-system) [Ref].

This results in endothelial dysfunction and multiple organ injuries including the heart, lungs, and kidneys.

This could also cause vascular permeability and exaggerated neutrophilic response resulting in ARDS (Acute respiratory distress syndrome).

Cardiovascular diseases in Coronavirus infection (COVID-19 infected patients):

To determine the prevalence and consequences of cardiovascular disorders in COVID-19 infection, data analysis is ongoing. However, until now, the following cardiovascular disease manifestations have been encountered.

• It causes the underlying coronary artery disease to worsen and raises the chance that the condition may kill you.
• COVID-19 infection has multiple direct and indirect cardiovascular complications. These include:
  • Fulminant myocarditis - This is the worst form of presentation and is fatal in the majority of infected patients.
  • Non-ST-elevation and ST-segment elevation Patients with SARS-CoV-2 infections have been documented to develop myocardial infarction (NSTEMI).
  • Cardiomyopathies (dilated cardiomyopathy) have been reported in patients who survived the acute cardiac insult.
  • Congestive cardiac failure may occur as a result of acute myocarditis or as a complication of ACS (Acute Coronary Syndrome).
  • Acute myocardial ischemia can lead to fatal cardiac arrhythmias, particularly polymorphic VT (ventricular tachycardia), ventricular fibrillation, and monomorphic VT.
  • Patients with COVID-19 infections are increasingly reporting thromboembolic events such as pulmonary emboli and strokes.
  • Cardiogenic shock may happen in the presence of fulminant myocarditis or severe ischemia damage.
• The burden of cardiovascular illnesses in COVID-19 infection may increase as a result of medications used to treat COVID-19 patients.
• Drugs like chloroquine, Hydroxychloroquine, and Azithromycin are used to treat patients with COVID-19 infection.
• These drugs are associated with a severe burden of cardiovascular illnesses in COVID-19 infection may increase as a result of medications used to treat COVID-19 patients. cardiovascular side effects such as QT-prolongation, cardiomyopathy, and conduction defects resulting in heart-blocks.

Should you discontinue ACE inhibitors or ARBs due to the risks of getting infected and the high mortality associated with COVID-19 infection?

This is the current hot button issue. However, as was previously mentioned, the consensus is to continue using ACE inhibitors, ARBs, and ARNI in patients with underlying left ventricular dysfunction and signs of congestive cardiac failure until recommendations are made by reputable organisations like the AHA (American Heart Association) and the ESC (European Society of Cardiology).

The ACE2 hypothesis is yet to be proved while these drugs have proven mortality benefits in systolic heart failure.

So Patients who are taking ACE inhibitors or ARBS/ARNI should continue their medication as advised.

Junyi Guo et al in their article termed it a double-edged sword [Ref].

The use of ACEIs/ARBs in COVID-19 may have two negative effects. On the one hand, there may be a higher chance of contracting SARS-CoV-2 as a result.

On the other side, it might lessen the extent of the infection's lung damage.

The SARS-CoV-2 infection may have an impact on the ratio of angiotensin II to angiotensin 1-7. ARB, angiotensin receptor blocker, ARDS, acute respiratory distress syndrome, AT1R, angiotensin II type 1 receptor, *indicates finding in hearts; ACE1, angiotensin-converting enzyme 1; ACE2, angiotensin-converting enzyme 2; ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; dotted line, speculation based

Investigations in Coronavirus infected Patients with Suspected Cardiovascular diseases:

When evaluating a left ventricular function, echocardiography and ECG are helpful. The presence of myocarditis would support the diagnosis of global left ventricular failure without localised wall motion abnormalities.

Other laboratory and imaging modalities with higher sensitivity and specificity include:

• Endomyocardial biopsy
• Indium 3 antimycin scintigraphy
• Cardiac CMR (Cardiovascular magnetic resonance imaging)
• Cardiac CT
• Cardiac biomarkers including:
  • Troponin T and Troponin I with high sensitivity (hsTNT and hsTNI). These also affect the prognosis of COVID-19 infections.
  • Brain natriuretic peptide (BNP) and Pro BNP

Treatment of Cardiovascular diseases in COVID-19 infections:

Treatment of fulminant myocarditis in patients with COVID-19 is as follows:

• Conventional treatment of Congestive cardiac failure including Oxygen, diuretics, nitrates, and ACE-inhibitors or ARBs.
• Intravenous immunoglobulins
• Systemic corticosteroids
• Tocilizumab (Interleukin-6 inhibitors) and other immune-modulators
• Antiviral agents such as Oseltamivir and Ritonavir-boosted Lopinavir (although these drugs have not been proven to have beneficial effects).

Left Ventricular assist devices such as:

• LVAD (left ventricular assist device),
• Impella (It is the only FDA-approved, non-surgical heart pump to temporarily assist the pumping function of the heart)
• ECMO (Extracorporeal membrane oxygenation)
• Tandem heart (It is a percutaneous implantable ventricular assistive device)

Prognosis of Cardiovascular diseases in Coronavirus infection

The mortality risk is 10 percent in patients with cardiovascular diseases and is highest in patients with underlying uncontrolled Diabetes Mellitus and Hypertension accounting for 7 to 10 percent of cases.

Future and Potential Therapies in COVID-19 infections:

There is a potential role of recombinant human ACE2 (rHACE) analogs in the treatment of COVID-19 infection.

The rHACE might block the entry of the virus into the cells by competitively inhibiting it.It might also avert conditions including myocardial fibrosis, diastolic dysfunction, and hypertension brought on by angiotensin II.