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\begin{document}

\title{The Evaluation of Myocardial Performance Index in Patients with
COVID-19: An Echocardiographic Follow-up Study''}



\author[1]{Hakan Kaya}%
\author[2]{Ramazan  Asoğlu}%
\author[3]{Abdulmecit Afşin}%
\author[1]{hakan tibilli}%
\author[1]{Ercan Kurt}%
\author[1]{Safiye Kafadar}%
\author[1]{Umut Gülaçtı}%
\author[1]{Hüseyin Kafadar}%
\affil[1]{Adiyaman University Faculty of Medicine}%
\affil[2]{Adiyaman Universitesi}%
\affil[3]{Adiyaman University}%


\vspace{-1em}



  
  \date{June 09, 2024}


\begingroup
\let\center\flushleft
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\selectlanguage{english}
\begin{abstract}
INTRODUCTION: The epidemic of pneumonia caused by a new coronavirus
disease 2019 (COVID-19) rapidly spread all over the world.
Pathophisyology of the cardiovascular effects of COVID-19 is still not
well known. Myocardial dysfunction may occur in cytokine-based immune
reactions. Myocardial performance index (MPI) is a feasible parameter
that reflects systolic and diastolic cardiac functions. We aimed to
evaluate the MPI in patients with COVID-19. METHODS: The study consisted
of 40 patients diagnosed with COVID-19 who had mild pneumonia and did
not need intensive care treatment. All patients underwent
echocardiographic evaluation. The MPI and laboratory parameters were
compared between the acute period of infection and after clinical
recovery in patients with COVID-19. RESULTS: Statistically significant
higher MPI (0.56\selectlanguage{ngerman}±0.09 versus 0.44±0.07, p\textless{}0.001), longer
isovolumic relaxation time (112.3 ±13.4 versus 91.8±12.1ms,
p\textless{}0.001), longer deceleration time (182.1 ± 30.6 versus 161.5
± 43.5ms, p=0.003), shorter ejection time (279.6±20.3 versus
298.8±36.8ms, p\textless{}0.001) and higher E/A ratio (1.53±0.7 versus
1.22±0.4, p\textless{}0.001), were observed during acute period of
infection compared to ones after clinical recovery. Compared with basal
values, no significant change in left ventricular (LV) systolic ejection
fraction was observed after clinical recovery (60.3 ± 3.2\% versus
61.7±2.4\%, p\textgreater{}0.05). CONCLUSION: Our study showed that
although, LV systolic function appear normal in COVID-19 patients, they
have globally reversible LV diastolic dysfunction, based on tissue
Doppler derived MPI. This could be due to isolated subclinical diastolic
dysfunction. The underlying mechanism and its clinical significance can
be established by further studies.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{The Evaluation of Myocardial Performance Index in Patients with
COVID-19: An Echocardiographic Follow-up Study}

\textbf{ABSTARCT}

\textbf{INTRODUCTION} The epidemic of pneumonia caused by a new
coronavirus disease 2019 (COVID-19) rapidly spread all over the world.
Pathophisyology of the cardiovascular effects of COVID-19 is still not
well known. Myocardial dysfunction may occur in cytokine-based immune
reactions. Myocardial performance index (MPI) is a feasible parameter
that reflects systolic and diastolic cardiac functions. We aimed to
evaluate the MPI in patients with COVID-19.

\textbf{METHODS} The study consisted of 40 patients diagnosed with
COVID-19 who had mild pneumonia and did not need intensive care
treatment. All patients underwent echocardiographic evaluation. The MPI
and laboratory parameters were compared between the acute period of
infection and after clinical recovery in patients with COVID-19.

\textbf{RESULTS} Statistically significant higher MPI (0.56\selectlanguage{ngerman}±0.09 versus
0.44±0.07, p\textless{}0.001), longer isovolumic relaxation time (112.3
±13.4 versus 91.8±12.1ms, p\textless{}0.001), longer deceleration time
(182.1 ± 30.6 versus 161.5 ± 43.5ms, p=0.003), shorter ejection time
(279.6±20.3 versus 298.8±36.8ms, p\textless{}0.001) and higher E/A ratio
(1.53±0.7 versus 1.22±0.4, p\textless{}0.001), were observed during
acute period of infection compared to ones after clinical recovery.
Compared with basal values, no significant change in left ventricular
(LV) systolic ejection fraction was observed after clinical recovery
(60.3 ± 3.2\% versus 61.7±2.4\%, p\textgreater{}0.05).

\textbf{CONCLUSION} Our study showed that although, LV systolic function
appear normal in COVID-19 patients, they have globally reversible LV
diastolic dysfunction, based on tissue Doppler derived MPI. This could
be due to isolated subclinical diastolic dysfunction. The underlying
mechanism and its clinical significance can be established by further
studies.

\textbf{Key words:} COVID-19, echocardiography, myocardial performance
index.

\textbf{INTRODUCTION}

Wuhan, China became the center of an epidemic of unknown pneumonia on
December, 3, 2019 (1-4). Blood samples, oral swabs, bronchoalveolar
lavage fluid, and anal swabs collected from patients with severe
pneumonia were analyzed. This novel pathogen, enveloped RNA
beta-coronavirus, was named severe acute respiratory syndrome
coronavirus 2 (5). Subsequently, the disease caused by this virus was
called coronavirus disease 2019 (COVID-19). COVID-19 has become a
life-threatening public health emergency internationally (6). COVID-19
typically presents with respiratory tract symptoms including fever, dry
cough, and dyspnea. The disease can progress to pneumonia and acute
respiratory distress syndrome (7). The physiopathology of COVID-19
infection is not clear. However, an extreme immune response and cytokine
storm are thought to have a pivotal roles in the etiopathogenesis of the
disease. Our knowledge of the cardiovascular effects of COVID-19 is
limited. Studies have reported that the left and right ventricular
ejection fractions may be reduced by a cytokine-mediated systemic
response to infections by increasing the end-diastolic and end-systolic
volumes of both ventricles (8). However, it is not known whether
systolic and diastolic dysfunction of the left ventricle (LV) develops
in patients with COVID-19.

Two-dimensional and Doppler echocardiography provide important
information about the diastolic and systolic function of the LV. The
myocardial performance index (MPI) is a reliable echocardiographic index
that combines diastolic and systolic measurements (9). We evaluated the
MPI of patients with COVID-19.

\textbf{METHODS}

\textbf{Study Population}

The present study consisted of fourty healthy control subjects and 40
patients diagnosed with COVID-19 who had mild pneumonia and did not need
intensive care treatment. Patients with atrioventricular conduction
disturbance, non-sinus rhythm on ECG, ventricular extra-systoles,
valvular heart disease, and a history of chronic heart failure, chronic
rheumatic heart disease, atrial dysrhythmia, a permanent cardiac
pacemaker, or acute coronary syndrome were excluded from the study. The
clinical history and laboratory data of patients and results of reverse
transcription-polymerase chain reaction (RT-PCR) of oropharyngeal swabs
were evaluated. All patients had a positive RT-PCR result. All patients
with COVID-19 were treated with vitamin C, hydroxychloroquine, and/or
favipravir. All participants were recruited from Ad\selectlanguage{polish}ı\selectlanguage{english}yaman University
Hospital. This study was conducted prospectively according to the
principles of the Declaration of Helsinki. The study protocol was
approved by the institutional medical ethics committee (2020/5-25).
Written informed consent was obtained from every participant.

\textbf{Echocardiographic Examination}

Transthoracic echocardiographic examination was performed in all
subjects using a Vivid 5S (GE Healthcare Systems, Horten, Norway) with a
2.0--3.5-MHz transducer. Transthoracic echocardiographic examination was
performed at the acute stage of infection and after clinical recovery in
patients with COVID-19. The recovery echocardiography exam was performed
on patients who were still hospitalised but had recovered
symptomatically and according to laboratory findings. The average time
interval between the baseline and recovery echocardiography exam was
about 28\selectlanguage{ngerman}±3,4 days. Doppler and Two-dimensional echocardiography were
done in the standard views according to the guidelines of the American
Society of Echocardiography (10). The modified Simpson's method was used
to calculate the left ventricular ejection fraction (LVEF) (11). We used
apical four-chamber views by putting the sample volume between the tips
of the mitral leaflets for the pulsed-wave Doppler recordings of the
mitral inflow velocities. The peak late (A) and early (E) transmitral
filling velocities and the ratio of transmitral early to late peak
velocities (E/A) were measured as conventional Doppler indices. The time
between closing the aortic valve and opening the mitral valve was
defined as the \selectlanguage{polish}ı\selectlanguage{english}sovolumic relaxation time (IRT). The time between
closing the mitral valve and opening the aortic valve was accepted as
the isovolumic contraction time (ICT). Ejection time (ET) was defined as
the time between opening and closing of the aortic valve on the LV out
flow velocity profile. Pulsed wave tissue Doppler imaging was performed
from an apical four-chamber view with a sample volume of 2 mm placed on
the medial wall of the mitral annulus. High frequency signals were
excluded by making filter settings. The scanning intervals of Doppler
ultrasound were obtained from the mitral annular velocity intervals. MPI
was calculated by using the equation: MPI=(ICT+IRT)/ET (12). Tissue
Doppler measurements were obtained from an average of five consecutive
cardiac cycles. The calculation of tissue Doppler-derived MPI is
presented in Figure 1.

\textbf{Laboratory Parameters}

Blood samples were studied on days 0, 7, 14, and 28. An
immunofluorescence assay was used to obtain COVID-19 antibody titers.
Respiratory secretions were sent for RT-PCR testing. Cardiac troponin I
(cTnI) was studied with Immulate (Bio, DPC) from blood samples. The
lactate dehydrogenase (LDH), creatinine kinase (CK), and creatinine
levels were analyzed using an Architect c8000 Chemistry System (Abbott
Diagnostics, Abbott Park, IL, USA) with commercial kits (Abbott
Diagnostics). Hemoglobin and complete white blood counts (WBC),
including neutrophil and lymphocyte counts, were measured using an
automated CELL-DYN Ruby hematology analyzer (Abbott Diagnostics) and
expressed as \selectlanguage{ngerman}×103 cells/mm3

\textbf{Statistical analysis}

SPSS v. 22.0 (Chicago, USA) was used for the analyses. Categorical
variables are presented as numbers and percentages, and were compared
with the Chi-square test. Continuous variables were tested for
distribution normality with the Kolmogorov--Smirnov test. Continuous
variables are presented as the mean±standard deviation. An independent
t-test or Mann--Whitney U-Test was used to compare the variables between
the two groups, as appropriate. The acute period of infection and
clinical recovery values were compared using the paired t-test if the
data were normally distributed. A P-value below 0.05 was considered
statistically significant.

\textbf{RESULTS}

This study enrolled 40 consecutive patients (26 males (65\%); mean age,
54±11 years) and 40 healthy control subjects (24 males (60\%); mean age,
52±13 years). The patients were admitted to hospital with a fever
\textgreater{}38ºC, cough, sore throat, rhinorrhea, shortness of breath,
headache, myalgia, diarrhea. The PCR test was positive in all patients.
The mean interval between the first echocardiogram and symptom onset was
9.3±5.5 days. The clinical characteristics including; age, gender,
smoking, hypertension, diabetes, systolic blood pressure, diastolic
blood pressure, heart rate were similar between the patients and healthy
control subjects (p\textgreater{}0.05, for all). ). Compared with the
healthy controls, patients with COVID-19 had a significant higher MPI
(0.56±0.09 versus 0.41±0.06, p\textless{}0.001), longer IRT (112.3±13.4
versus 90.6±11.2ms, p\textless{}0.001), longer deceleration time
(182.1±30.6 versus 160.8±42.7ms, p=0.003), shorter ET (279.6±20.3 versus
299.6±34.7ms, p\textless{}0.001) and higher E/A ratio (1.53±0.7 versus
1.21±0.3, p\textless{}0.001). LVEF was similar in the patients with
COVID-19 and healthy controls (60.3±3.2\% versus 61.9±4.8\%,
p\textgreater{}0.05). ICT was similar in both groups (44.3±7.8 versus
41.8±8.7ms, p\textgreater{}0.05). Compared with the healthy controls,
the patients with COVID-19 had a significantly higher cTnI (0.96±0.12
versus 0.10±0.01 ng/ml, p\textless{}0.001), LDH (486.8±118.6 versus
316.4±108.9 IU/L, p=0.002) WBC (12.3±4.7 versus 7.0±2.6
10\textsuperscript{3}/\selectlanguage{greek}µ\selectlanguage{english}l, p\textless{}0.001), neutrophil count (9.7\selectlanguage{ngerman}±6.2
versus 4.2±1.5 10\textsuperscript{3}/\selectlanguage{greek}µ\selectlanguage{english}l, p\textless{}0.001) and lower
lymphocyte count (0.9\selectlanguage{ngerman}±0.2 versus 2.8±0.6 10\textsuperscript{3}/\selectlanguage{greek}µ\selectlanguage{english}l,
p\textless{}0.001). The creatinine, CK and hemoglobin levels were
similar in both groups (p\textgreater{}0.05, for all). Table 1
summarizes the clinical characteristics and laboratory and
echocardiographic findings of the study groups.

The systolic and diastolic blood pressure and heart rate were similar
between the acute period of infection and after clinical recovery
(p\textgreater{}0.05, for all). Compared with the acute period of
infection in patients with COVID-19, after clinical recovery there was a
significantly lower MPI (0.44\selectlanguage{ngerman}±0.07 versus 0.56±0.09, p\textless{}0.001),
shorter IRT (91.8±12.1 versus 112.3±13.4ms, p\textless{}0.001), shorter
deceleration time (161.5±43.5 versus 182.1±30.6ms, p=0.003), longer ET
(298.8±36.8 versus 279.6±20.3ms, p\textless{}0.001) and lower E/A ratio
(1.22±0.6 versus 1.53±0.7, p\textless{}0.001). ). LVEF was similar in
the acute period of infection and after clinical recovery (60.3±3.2\%
versus 60.7±3.8\%, p\textgreater{}0.05). ICT was similar in the acute
period of infection and after clinical recovery (44.3±7.8 versus
40.6±9.7ms, p\textgreater{}0.05). Compared with the acute period of
infection in patients with COVID-19, after clinical recovery there was a
significantly lower cTnI (0.11±0.08 versus 0.96±0.12 ng/ml,
p\textless{}0.001), LDH (334.5±110.9 versus 486.8±118.6 IU/L, p=0.004),
WBC (7.2±3.1 versus 12.3±4.7 103/\selectlanguage{greek}µ\selectlanguage{english}l, p\textless{}0.001), neutrophil
count (4.5\selectlanguage{ngerman}±1.8 versus 9.7±6.2 10\textsuperscript{3}/\selectlanguage{greek}µ\selectlanguage{english}l,
p\textless{}0.001) and higher lymphocyte count (2.1\selectlanguage{ngerman}±0.4 versus 0.9±0.2
10\textsuperscript{3}/\selectlanguage{greek}µ\selectlanguage{english}l, p\textless{}0.001). The creatinine, CK and
hemoglobin levels were similar between the acute period of infection and
after clinical recovery (p\textgreater{}0.05, for all). Table 2 gives
the clinical characteristics, laboratory and echocardiographic findings
of the patients with COVID-19 in the acute period of infection and after
clinical recovery.

\textbf{DISCUSSION}

This is the first echocardiographic follow-up study to evaluate the
systolic and diastolic function of the left ventricle in COVID-19
patients. Our data showed that LV performance was impaired subclinically
during the acute period of COVID-19 and this impaired performance
recovered with clinical improvement.

Since the first case was reported at the end of 2019, the COVID-19
outbreak has become a pandemic. The high transmission ratio of the virus
has made it a threat to public health globally (13,14). Coronaviruses
are non-segmented positive-sense RNA viruses that are broadly
distributed in humans and other mammals, such as camels, bats, mice,
dogs, and cats. (15). Coronaviruses can cause respiratory, enteric,
cardiovascular, and neurological diseases (16-19). The most common
symptoms of COVID-19 are fever (in 88.7\% of patients) and a dry cough
(in 67.8\% of patients), followed by headache, fatigue, or shortness of
breath. The overall mortality rate is 2.3\% and those with pre-existing
comorbid conditions have higher case mortality rates: diabetes 7.3\%,
chronic respiratory disease 6.3\%, hypertension 6.0\% cardiovascular
disease 10.5\%, and cancer 5.6\% (20).

We assessed the left ventricular diastolic and systolic function using
several echocardiographic parameters. Although systolic and diastolic
dysfunction appear together, there are few Doppler echocardiogram
variables that combine systolic and diastolic measurements. We used the
MPI, which includes the systolic contraction and diastolic relaxation
periods of the left ventricle (21). MPI is not significantly affected by
pre-load, afterload, sample volume location, age, or rhythm (22,23).
Therefore, it is a reliable index. The value of MPI in left ventricular
dysfunction has been confirmed in patients with symptomatic heart
failure with non-ischemic or ischemic etiology and idiopathic dilated
cardiomyopathy (21, 22). In the present study, MPI was higher in the
acute disease period in the patients with COVID-19, but regressed
significantly after clinical recovery.

The pathophysiological and cardiovascular effects of COVID-19 are not
clear. However, the disease is thought to be associated with an
excessive immune response triggered by the virus. Studies have found
that COVID-19 patients have high levels of interleukin (IL)-1 beta,
IL-6, interferon gamma, and monocyte chemoattractant protein-1, which
probably led to an activated T-helper-1 cell response (7). Studies of
coronavirus and influenza outbreaks suggest that viral infections can
trigger a systemic inflammatory response that causes acute coronary
syndromes, arrhythmias, and heart failure (23-26). Similarly, underlying
cardiovascular diseases may be exacerbated or new cardiac pathologies
may be induced during COVID-19. Acute coronary events may be due to
increased myocardial demand triggered by infections that accelerate
myocardial damage or infarction. Alternatively, circulating cytokines
released during severe systemic inflammatory stress may cause
instability and rupture of atherosclerotic plaque. Patients with heart
failure are also prone to hemodynamic decompensation during the stress
of severe infections. During most influenza outbreaks, more patients die
of cardiovascular causes than from pneumonia (27). COVID-19 causes
myocardial inflammation and myocarditis (28-30). In our patients, the
elevated cTnI might reflect the myocardial damage. cTnI is part of the
contractile apparatus in cardiomyocytes and is expressed only in the
heart (31). As a result of its organ specificity, cTnI can be used to
diagnose cardiomyocyte damage (32). The elevated LDH might reflect the
tissue damage and inflammation (33). We assumed that the temporary
impairment in echocardiographic parameters in the acute phase was caused
by proinflammatory mediators, such as tumor necrosis factor (TNF) and
the IL-1 and -6 families of cytokines, which have significant negative
inotropic effects (34). Myocardial function may also be impaired with
direct COVID-19 myocyte infection, leading to active myocarditis.
Reported data on the severity, extent, and short- and long-term
cardiovascular effects of COVID-19 are limited. Our study has
limitations. The main study limitation is the small sample size. Another
limitation is that the circulatory levels of cytokines such as IL-1,
IL-6, and TNF could not be measured. Further studies that measure the
circulatory levels of these cytokines and echocardiographic variables
are needed based on the current hypothesis of cytokine-mediated
temporary impairment of left ventricular performance.

In conclusion, our study showed that although, LV systolic function
appear normal in COVID-19 patients, they have globally reversible LV
diastolic dysfunction, based on tissue Doppler derived MPI. This could
be due to isolated subclinical diastolic dysfunction. The underlying
mechanism and its clinical significance can be established by further
studies.

\textbf{Conflict interests:} The authors declare that they have no
competing interests.

\textbf{Funding} : This study received no grant funding from any agency
in the public, commercial or not-for-profit sectors.

\textbf{Acknowledgements} : Our article has been accepted as a e-poster
presentation in EACVI -- Best of Imaging 2020 (Number: 90512).

\textbf{Availability of data and materials:} The datasets used and/or
analyzed during the current study are available from the corresponding
author on reasonable request.

\textbf{Author contributions:} Concept/design: HK, UG, HT, EK, Data
analysis/interpretation: HK, HT, EK, Drafting article: AA, RA, EK, SK,
Critical revision of article: AA, RA, Approval of article: HK, RA, HT,
AA, UG, EK, SK, HK, Statistics: HK, UG, Funding: HK, EK Data collection:
HK.

\textbf{REFERENCES}

\begin{enumerate}
\tightlist
\item
  Wang C, Horby PW, Hayden FG, et al. A novel coronavirus outbreak of
  global health concern. Lancet 2020; 395: 470-3.
\item
  Hsu LY, Chia PY, Vasoo S. A midpoint perspective on the COVID-19
  pandemic. Singapore Med J 2020;
\item
  Lum LHW, Tambyah PA. Outbreak of COVID-19 - an urgent need for good
  science to silence our fears? Singapore Med J 2020;61(2):55-7
\item
  Kok SXS, Shah MT, Cheong WK, et al. Dealing with COVID-19: initial
  perspective of a small radiology department. Singapore Med J 2020;
\item
  Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology
  of 2019 novel coronavirus: implications for virus origins and receptor
  binding. Lancet 2020; 395: 565-74.
\item
  Ksiazek TG, Erdman D, Goldsmith CS, et al. A novel coronavirus
  associated with severe acute respiratory syndrome. N Engl J Med 2003;
  348: 1953-66.
\item
  Huang C,Wang Y, Li X, et al. Clinical features of patients infected
  with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395:
  497-506.
\item
  Parrillo JE. Pathogenetic mechanism of septic shock. N Engl J Med
  1993; 328:1471--77.
\item
  Tei C: New non-invasive index for combined systolic and diastolic
  ventricular function. J Cardiol 1995; 26: 135-6.
\item
  Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the
  Evaluation of Left Ventricular Diastolic Function by Echocardiography:
  An Update from the American Society of Echocardiography and the
  European Association of Cardiovascular Imaging. J Am Soc Echocardiogr.
  2016;29(4):277-314.
\item
  Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for Cardiac
  Chamber Quantification by Echocardiography in Adults: An Update from
  the American Society of Echocardiography and the European Association
  of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015; 28: 1-39.
\item
  Tei C, Nishimura RA, Seward JB, et al. Noninvasive Doppler derived
  myocardial performance index: correlation with simultaneous
  measurements of cardiac catheterization measurements. J Am Soc
  Echocardiogr 1997; 10: 169--78.
\item
  World Health Organization. Pneumonia of unknown cause---China.
  Accessed January 5,
  2020.https://www.who.int/csr/don/05-january-2020-pneumonia-of-unkown-cause-china/en/
\item
  World Health Organization. Novel coronavirus---China. Accessed January
  12, 2020. https://www.who.int/csr/don/12-january-2020-
  novel-coronavirus-china/en/
\item
  Su S, Wong G, Shi W, et al. Epidemiology, genetic recombination, and
  pathogenesis of coronaviruses. Trends Microbiol 2016; 24: 490--502.
\item
  Yin Y, Wunderink RG. MERS, SARS and other coronaviruses as causes of
  pneumonia. Respirology 2018; 23: 130-37.
\item
  Drosten C, G\selectlanguage{ngerman}ünther S, Preiser W, et al. Identification of a novel
  coronavirus in patients with severe acute respiratory syndrome. N Engl
  J Med 2003; 348: 1967-76.
\item
  Zaki AM, van Boheemen S, Bestebroer TM, et al. Isolation of a novel
  coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med
  2012; 367: 1814-20.
\item
  Weiss SR, Leibowitz JL. Coronavirus pathogenesis. Advances in virus
  research 2011; 81: 85-164.
\item
  Wu Z, McGoogan JM. Characteristics of and Important Lessons From the
  Coronavirus Disease 2019 Outbreak in China: Summary of a Report of
  72314 Cases From the Chinese Center for Disease Control and
  Prevention. JAMA 2020; 323: 1239-42.
\item
  Dujardin KS, Tei C, Yeo TC, et al. Prognostic value of a Doppler index
  combining systolic and diastolic performance in idiopathic-dilated
  cardiomyopathy. Am J Cardiol 1998; 82: 1071--76.
\item
  Harjai KJ, Scott L, Vivekananthan K, et al. The Tei index: a new
  prognostic index for patients with symptomatic heart failure. J Am Soc
  Echocardiogr 2002; 15: 864--8.
\item
  Madjid M, Miller CC, Zarubaev VV, et al. Influenza epidemics and acute
  respiratory disease activity are associated with a surge in
  autopsy-confirmed coronary heart disease death: results from 8 years
  of autopsies in 34,892 subjects. Eur Heart J 2007; 28: 1205-10.
\item
  Kwong JC, Schwartz KL, Campitelli MA, et al. Acute myocardial
  infarction after laboratory-confirmed influenza infection. N Engl J
  Med 2018; 378: 345-53.
\item
  Madjid M, Connolly AT, Nabutovsky Y, et al. Effect of high influenza
  activity on risk of ventricular arrhythmias requiring therapy in
  patients with implantable cardiac defibrillators and cardiac
  resynchronization therapy defibrillators. Am J Cardiol 2019; 124: 44-
  50.
\item
  Kytömaa S, Hegde S, Claggett B, et al. Association of influenza-like
  illness activity with hospitalizations for heart failure: the
  Atherosclerosis Risk in Communities Study. JAMA Cardiol 2019; 4:
  363-9.
\item
  Madjid M, Casscells SW. Of birds and men: cardiologists' role in
  influenza pandemics. Lancet 2004; 364: 1309.
\item
  Sala S, Peretto G, Gramegna M, et al. Acute myocarditis presenting as
  a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory
  infection. Eur Heart J. 2020,41(19):1861--2.
\item
  Zhou R. Does SARS-CoV-2 cause viral myocarditis in COVID-19 patients?
  Eur Heart J 2020;41:2123.
\item
  Shi S, Qin M, Shen B, et.al. Association of Cardiac Injury With
  Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA
  Cardiol. 2020 Mar 25 : e200950.
  https://doi.org/10.1001/jamacardio.2020.0950
\item
  Reichlin T, Hochholzer W, Bassetti S, et al. Early diagnosis of
  myocardial infarction with sensitive cardiac troponin assays. N Engl J
  Med 2009; 361: 858--67.
\item
  Keller T, Zeller T, Ojeda F, et al. Serial changes in highly sensitive
  troponin I assay and early diagnosis of myocardial infarction. JAMA
  2011; 306: 2684 --93.
\item
  Lee N, Hui D, Wu A, et al. A major outbreak of SARS in Hong Kong. N
  Engl J Med 2003; 348: 1986--94.
\item
  Mann DL. Inflammatory mediators and the failing heart: past, present
  and the foreseeable future. Circ Res 2002; 91:988--98.
\end{enumerate}

\textbf{Figure legend}

Figure 1. Calculation of tissue Doppler derived left ventricular
myocardial performance index.

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