Left Ventricular Global Longitudinal Strain by Speckle Tracking Echocardiography in Pregnant COVID-19 Patients

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Justification
A new COVID-19 infection caused by SARS-CoV-2 emerged at the end of 2019. In addition to the known respiratory manifestations of COVID-19, the virus has multi-organ tropism, affecting the cardiovascular system [1, 2].
The described mechanisms of heart damage include: a direct viral effect on the myocardium, mediated, realized through systemic inflammation, a decrease in myocardial perfusion, destabilization of atherosclerotic plaques, catecholamine hyperstimulation, which is realized, incl. form of stress cardiomyopathy [2].
TTE is an initial imaging modality for assessing cardiac manifestations of COVID-19, which is useful for assessing myocardial health [3]. Evaluation of LVGLS using STE provides an objective quantitative assessment of longitudinal myocardial deformity, allowing timely detection of subclinical myocardial dysfunction, which contributes to the correction of therapy as close as possible to real time [4]. In our study, we studied the effect of COVID-19 on LVGLS indicators in pregnant women, regardless of the severity of the manifestation and course of the new coronavirus infection.

Methods
Analyzed the data of 102 pregnant patients, whose average age was 31.8 ± 5.9 years, hospitalized in the maternity hospital at GKB No. 15 named after. O. M. Filatov DZM with a clinical picture of a new coronavirus infection and a positive test result for SARS-CoV-2, who underwent TTE and STE at admission and before discharge. 12 patients were not included in the study due to poor visualization of the left ventricular myocardium.
All patients (100%) in our study had sinus rhythm and a comparable mean heart rate. The insufficient size of the acoustic window was an exclusion criterion, since the most important task was to obtain the optimal gray-scale image.
TTE in monitoring mode was performed on ultrasound scanners Vivid E95 (GE, USA), Aplio 500 (Canon Medical, Japan). TTE was performed according to a standard protocol with an assessment of the size of cavities, intracardiac hemodynamics, systolic and pumping functions of the heart. For STE, GLS was assessed. Cine loops were formed based on the 16-segment LV model according to R. Lang [5]. The GLS results were presented as the absolute value of the parameter (Fig. 1a, b).
The results were statistically analyzed using 9.3 software (SAS institute Inc., Cary, NC). Descriptive statistics are presented as a proportion or mean range of probable deviation. Comparisons between groups were made using Chi-square or Fisher's exact test for categorical variables and Wilcoxon's rank sum test for continuous variables. Differences were considered statistically significant at p <0.05.

results
Of 114 patients with positive PCR for COVID-19, 100 patients were included in the analyzed groups (correct tracing). Group 1 (Table 1) included 52 patients without a history of cardiovascular disease, however, after in-depth questioning, 2 patients were transferred to Group 2, which eventually numbered 50 patients (pregnancy-associated pathology: chronic arterial hypertension, gestational diabetes mellitus).
The average age of patients in group 1 was 32.1 ± 5.3 years, and in group 2 - 30.9 ± 7.2 years.
The average value of ventricular volumes (EDV, CVV) in both groups was normal and did not differ significantly from the control group. LVEF in both groups was also normal, which made it impossible to distinguish between groups in this parameter, and also partially misled clinicians about normal LV function.
Thus, we did not see differences between the groups of patients with COVID-19 in the non-invasive parameters of LV pre- and afterload.
The average heart rate did not differ between the groups and was 95.0 ± 8.3 bpm and 92.0 ± 9.0 bpm.
The mean stroke volume (SV) did not differ between groups and did not differ from normal values. When analyzing the indicators of the pumping function of the heart, it was noted that the CO value in the 1st group was 6.3 ± 0.53 L / min and this significantly exceeded the indicators of the control group, but was associated with an increase in heart rate against the background of hyperthermia, and not with a significant increase in stroke volume. The SV value in the 2nd group was 6.0 ± 0.7 L / min, which was also due to a positive chronotropic effect, rather than an increase in SV.
The average LVGLS value in the 1st group was -19.6 ± 0.45, which was significantly higher than the parameters of the 2nd group, which amounted to -13.4 ± 1.5.
When analyzing the data obtained, we revealed significant differences between the groups only in the value of LVGLS, while in patients of the 2nd group the LVGLS indices were significantly reduced relative to the reference values.

Discussion
Evaluation of myocardial biomechanics [6, 7] has repeatedly proved the low informative value of ejection fraction in predicting outcomes in patients without systolic dysfunction of the heart.
Today, modern markers of subclinical myocardial dysfunction of both the left and right ventricles are designated based on the assessment of the dynamics of STE data, reflecting the movement of myocardial fibers in the longitudinal, circular and radial directions [6, 8-16].
Before starting the study, we assumed the possibility of detecting LV dysfunction even with routine TTE, however, the overwhelming majority of the pregnant women examined by us, including those included in our protocol, had normal indicators of LV anatomy and function detected by TTE.
STE today is practically the only tool for detecting subclinical systolic dysfunction of the LV myocardium. In our study, there was no latent dysfunction of LV cardiomyocytes in women without a history of extragenital pathology, i.e. we obtained normal mean LVGLS values ​​against the background of normal LVEF.
However, we noticed that the mean LVGLS value in pregnant women with COVID-19 and a history of extragenital pathology (predominantly arterial hypertension), in the presence of preserved LVEF, was lower than the reference mean LVGLS value for a normal healthy population.
The decrease in LVGLS in COVID-19 can be due to several components of direct and indirect effects on the myocardium. The direct mechanism is viral myocardial infiltration, leading to inflammation and death of cardiomyocytes. An indirect effect is realized through systemic inflammation and oxidative stress [2, 17]. The main links of myocardial damage in COVID-19 are inflammatory mechanisms and activation of the immune response against the background of atherosclerosis, heart failure, and arterial hypertension [17], and in our study, almost 50% of the participants had a history of arterial hypertension (group 2).
It is known that a decrease in the level of LVGLS has an unfavorable prognostic value of cardiovascular events in the immediate and long-term period, including heart failure, regardless of the value of LVEF, age, sex, and the presence of arterial hypertension [18].
GLS as an independent predictor can predict mortality from all cardiovascular events, with the predictive power being most significant in patients with normal or moderately reduced LVEF [19]. These pregnant women may benefit from long-term follow-up after recovery from infection to monitor long-term outcomes such as heart failure, arrhythmias, or LV dysfunction.
Given the risk of transmission of COVID-19, routine use of STE is not recommended, however, in the event of clinical deterioration, the assessment protocol in pregnant women with COVID-19 should include targeted screening to reduce the viral load of the physician performing TTE while obtaining the maximum amount of information [20] ...
There are several limitations of this study that should be noted: a relatively small sample within a single medical institution in Moscow; lack of data on the Negroid and Mongoloid races. It also requires a special study of the problem of female and male fertility in the near and distant period after suffering a new coronavirus infection [21, 22] and issues of protecting the health of children born in the context of the COVID-19 pandemic.

Conclusion
In pregnant patients with COVID-19 without a history of cardiovascular pathology, we did not reveal a decrease in LVGLS indices against the background of normal LVEF. In patients of the 2nd group, against the background of normal values ​​of LVEF, there was a decrease in the value of LVGLS.
The reported low LVGLS values ​​in Group 2 likely reflect changes caused by factors not related to COVID-19. Similar changes have already been described by us earlier in patients with pregnancy pathology and extragenital pathology (preeclampsia, etc.) without COVID-19. Thus, in our study, we did not find instrumental signs of direct damage to the LV myocardium during COVID-19 in pregnant women.
Determination of markers of subclinical dysfunction of the left ventricular myocardium in pregnant women using LVGLS analysis may be important for identifying groups of patients who need long-term individual rehabilitation after undergoing COVID-19.

About the authors

Dmitriy A. Doroshenko

O.M. Filatov Municipal Clinical Hospital No. 15; Pirogov Russian National Research Medical University

Email: DrDoroshenko@mail.ru
ORCID iD: 0000-0001-8045-1423
SPIN-code: 9451-7029

MD, PhD

Россия, 23, Veshnyakovskaya str., 111539, Moscow; Moscow

Yuriy I. Rumyantsev

O.M. Filatov Municipal Clinical Hospital No. 15

Email: rumyantsev5@mail.ru
ORCID iD: 0000-0002-6210-3908
SPIN-code: 1745-3929
Россия, 23, Veshnyakovskaya str., 111539, Moscow

Olga V. Konisheva

O.M. Filatov Municipal Clinical Hospital No. 15

Email: OKonysheva@mail.ru
ORCID iD: 0000-0002-8064-2761

MD, PhD

Россия, 23, Veshnyakovskaya str., 111539, Moscow

Alla S. Samorukova

O.M. Filatov Municipal Clinical Hospital No. 15

Email: allareva82@mail.ru
ORCID iD: 0000-0002-3369-2600
SPIN-code: 7965-9149
Россия, 23, Veshnyakovskaya str., 111539, Moscow

Valeriy I. Vechorko

O.M. Filatov Municipal Clinical Hospital No. 15

Email: gkb15@zdrav.mos.ru
ORCID iD: 0000-0003-3568-5065
SPIN-code: 3192-2421

MD, PhD, Associate Professor

Россия, 23, Veshnyakovskaya str., 111539, Moscow

Leyla V. Adamyan

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Author for correspondence.
Email: adamyanleila@gmail.com
ORCID iD: 0000-0002-3253-4512

MD, PhD, Professor, Academician of the Russian Academy of Sciences

Россия, Moscow

References

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