key: cord-0752130-49mantab
authors: Harikrishnan, S.; Mohanan, P.P.; Chopra, V.K.; Ambuj, Roy; Sanjay, G.; Manish, Bansal; Chakraborty, R.N.; Chandra, Sharad; Chattarjee, S.S.; Chopra, H.K.; Mathew, Cibu; Deb, P.K.; Goyal, A.; Goswami, K.C.; Gupta, R.; Guha, S.; Gupta, V.; Hasija, P.K.; Wardhan, Harsh; Jabir, A.; Jayagopal, P.B.; Kahali, D.; Katyal, V.K.; Kerkar, P.G.; Khanna, N.N.; Majumder, B.; Mandal, M.; Meena, C.B.; Naik, N.; Narain, V.K.; Pathak, L.A.; Ray, S.; Roy, D.; Sarma, D.; Shanmugasundaram, S.; Singh, B.P.; Tyagi, S.K.; Venugopal, K.; Wander, G.S.; Yadav, R.; Das, M.K.
title: Cardiological society of India position statement on COVID-19 and heart failure
date: 2020-05-13
journal: Indian Heart J
DOI: 10.1016/j.ihj.2020.04.012
sha: ab506440ea3a3bba8fc891913c17fd7c592b0f1f
doc_id: 752130
cord_uid: 49mantab

The COVID 19 global pandemic has engulfed humanity with a huge impact on health systems across the world. Many patients develop myocardial injury which can lead to significant cardiovascular complications including HF. This will require aggressive management strategies which are evolving. Guideline directed drug therapy including ACEI/ARB/ARNI is to be continued in patients with pre-existing HF. Long-term cardiovascular effects of COVID-19 are yet to be ascertained. Protection of health care personnel from contracting the disease should be given high priority.

The COVID-19 pandemic has emerged as an unprecedented health emergency which has gripped the world. With nearly2 million cases and 140,000 deaths reported worldwide as of April 18, 2020 1 ,it has shattered the health systems in all the major economies of the world. Mankind is facing a crisis unheard of in its history. Government of India acted early andinitiated a nationwide lockdown on 25th

March 2020, which has resulted in slowing the spread of the virus, as ofApril 18 th 3 .The problem is that it has much more infectivity 4 which leads to exponential spread and that is why it is more dangerous than the other two 5 .

The majority (80%)of people with COVID-19 are either asymptomatic or have mild symptoms of a respiratory infection (fever, sore throat andcough)and make a full recovery. The mortality in COVID- 19 increases with the age of the patient. Though the mortality is less than 1% in <50 years, it reaches 15% in those >80 years 6 . This could be due to the loss of immunity and the presence of co-morbidities in older age.What has been observedin several affected countries is that people with diabetes, hypertension and heart disease including heart failure are at risk of a more severe illness.

In this position statement we will discuss the current understanding of the inter-relation between heart failure (HF) and COVID-19.There is no large data onpatients developingHF as a complication of the viral infection or the effect of COVID-19 onpatients with pre-existing heart failure.

The guidance provided in this position statement is based mostly on expert opinion which stands on the limitedpublished data, coming mostly from China and Europe. The knowledge on COVID-19 is rapidly evolving and the guidance will need periodic review.

1. 

Cardiac injury seems to occur in about 20-30% of hospitalized patients andcardiac complicationscontribute to 40% of deaths related to COVID-19 9,10, 11,12 .The incidence of acute cardiac injury was about 13 folds higher in ICU patients compared to non-ICU patients as reported by Li et al. 8 .In a series of 191 patients, acute cardiac injury was seen in 17% of the whole group, while it was 59% among those patients who died and 1% in survivors 13 . The mortality risk attributed to acute cardiac injury was found to be much more significant than that ofage, diabetes, COPDor prior CVD history 9,11,12 . Any of the above mechanisms which causes cardiac injury can potentially lead to heart failure. Also, the hemodynamic stress and inflammatory milieu can worsen pre-existing heart failure.

Heart Failure in COVID-19.

Zhou et al. in a series of 191 patients found that 23% of the overall cohort had heart failure; while HF was present in 52% of those who died,but only in 12% among those who survived 13 . This report points to the fact that HF is an important prognostic marker, but the criteria used todefine HFin this study was not provided. In another study ofa cohort of 799 patients from China,HF was identified as a complication in 49%of patients who died vs3% in those who recovered. This patient population had a baseline prevalence of HF <1% 20 indicating that most of the cases were due to the effect of COVID- 19 and not due to worsening of pre-existing HF.Patients with HF and COVID-19 aremostly male 21 .

Most of the patients with heart failure were noted to have lymphopenia and alsohigh levels of CRP 21 .

Although there are isolated reports of depressed ventricular function 1822 in COVID-19, the majority of patients with uncomplicated lymphocytic myocarditis presented with near normal systolic function 17 , 12 . Performing echocardiography has technical difficulties and limited by the availability of PPE, hencethere is no large data to say whethermyocarditis in COVID-19 presents as heartfailure with preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF).It is possible thatthe presentation as HFpEF may be more common 12 .

Patients with COVID-19 present with predominantly respiratory symptoms like cough and dyspnoea and can masquerade as worsening heart failure or acute decompensated heart failure (ADHF). This is especially true since heart failure patients may not mount fever. Cardiac symptoms like chest painand palpitations lack specificity. Fatigue is also reported.

comorbidities. This is to have a baseline status and to assess the QTc. QTc may be useful as the patient may be prescribed drugs like chloroquine and azithromycin, both of which increase QT interval. The most common ECG abnormalities reported in patients with COVID-19 with troponin elevation are ST segment depression, T-wave inversion and occasionally Q waves 11 .These changes may not be specific to any coronary territory, but may be diffuse. ST-segment elevation is also reported in patients with myocarditis or Takotsubo (stress) cardiomyopathy 18 .ECG may show arrhythmias like sinus tachycardia and atrial fibrillation. Though AF is the most common arrhythmia,malignant ventricular arrhythmias and bradyarrhythmia are also rarely reported 23, 24 .

Extensive ST elevation and heart blocks indicate poor prognosis.

Since there is significant risk involved to the personnel, echocardiogram should be ordered only if it is expected to change the course of management. Echocardiogram may reveal wall-motion abnormalities and give an idea about the global LV function. Both regional and global LV dysfunction have been reported in patients with COVID-19.

We don't have large data on MR findings in COVID-19 myocarditis. The following were reported in CMR in one of the patients with myopericarditis who had ventricular systolic dysfunction : increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, marked biventricular myocardial interstitial edema, and diffuse late gadolinium enhancement involving the entire biventricular wall 18 Cardiological Society of India recommends fibrinolytics and pharmacological therapy as treatment of choice in stable STEMI. 26 .

Biomarkers give important clues to the diagnosis and aid in the management of COVID-19patients.

The most evaluated biomarker is Troponin 27 The most common scenario is a mild elevation of troponin -this will persist throughout the course of the illness below the 99 th percentile of the normal and such patients have a good prognosis 29 .

Progressive elevation as described above carries a worse prognosis.Moderate elevation which tend to show a fall during the course of the illness indicates ACS or myocarditis.

If the rise in hs-cTnI tracks with the other inflammatory biomarkers (D-dimer,ferritin, interleukin-6 (IL-6),lactate dehydrogenase), it reflectsa possibility of a cytokine storm more than an isolated myocardial injury whereonly troponin is elevated 29 .

When HF is clinically suspected,serum natriuretic peptide levels (BNP or NT Pro BNP) should be assessed for aiding diagnosis and also to obtain prognostic information. Elevated NP have been Telemedicine links should be established which allows patients to contact health care personnel when there is a lock-down and there are restrictions in public transport. Also, the government should ensure smooth function of emergency services in hospitals which cater to acute coronary syndromes and acute decompensated heart failure.

COVID-19 patients who are diagnosed as having asymptomatic left ventricular systolic dysfunction or clinically overt heart failure should receive standard guideline directed therapy.Careful management of fluid balance, careful monitoring of electrolytes and renal function is very important.Another cardiovascular co-morbidity which can co-exist is venous thromboembolism and adequate prophylactic measures need to be undertaken 13 . NSAIDs like ibuprofen should be avoided 31 and paracetamol may be the preferred analgesic.

Personal protection: Caregivers should understand the responsibility of protecting themselvesfrom getting infected.Therefore, it is crucial that allhealthcare personnel caring for suspected and known COVID-19 patients must always observe all necessary precautions. All the personnel should be trained in using PPE (Personal protective equipment)in accordance with the existing guidelinesof MOHFW, Govt. of India.

Health 

It is imperative to optimize volume status very carefully with less aggressive fluid resuscitation for hypotension in patients with COVID and HF. Diuretics are to be used very carefully. Many a times it will be difficult to differentiate ARDS from pulmonary congestion. Non-invasive ventilation may be avoided as itgenerates aerosols.

SARS-CoV-2 binds to ACE2 before entering human cells, and there is a theoretical potentialfor worsening of the clinical status in patients who are on ACEI / ARB, due to upregulation of ACE2 A detailed table of drug interaction and precautions is attached. QT prolongation by HCQ,especially when combined with Azithromycin which is recommended as a treatment regimen, is of concern. All patients especially those with structural heart diseases are advised to have a baseline ECG to assess the QTc.

Patients who develop severe ventricular dysfunction and cardiogenic shock should be treated by inotropes and ventilatory support if required. Antiviral therapy and antibiotics are usually given.

There are reports of a therapeutic approach usingintravenous immunoglobulin and steroids, following whichejection fraction and cardiac biomarkers normalized in few weeks 1722 .. The regimen included the following -methylprednisolone as anti-inflammatory agent at 200 mg/day x 4 days,immunoglobulin to regulate immune status (20 g/day x 4 days), norepinephrine to raise blood pressure, diuretic (torsemide and furosemide) to reduce cardiac load and milrinoneas positive inotrope 17 .Another case-report mentions use of ECMO (extracorporeal membrane oxygenator), intravenous immunoglobulin, steroids, anti-viral therapy and renal replacement therapy in a COVID-19patient, who ultimately showed recovery of ventricular function. 22 .However, considering the high cost involved with and limited availability of advanced techniques like ECMO it should be used very sparingly in critical states.

Heart transplant recipients are not at high risk of contracting COVID -19 as per one report from China where they followed up 87 heart transplant patients. 44 . In another reportof two heart transplant recipients who contracted COVID-19, both survived and were treated with antibiotics and antivirals, while the sicker patient required cessation ofimmunosuppression, along with treatment with methylprednisolone and IVIG. 45 

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