key: cord-0831867-2s0w5fio
authors: Mercedes, Brisandi Ruiz; Serwat, Ayna; Naffaa, Lena; Ramirez, Nairovi; Khalid, Fatima; Steward, Sofia B.; Caro Feliz, Omar Gabriel; Kassab, Mohamad; Karout, Lina
title: New-Onset myocardial injury in COVID-19 Pregnant Patients: A Case Series of 15 Patients
date: 2020-10-22
journal: Am J Obstet Gynecol
DOI: 10.1016/j.ajog.2020.10.031
sha: 77f27e9d82ba9eb934fe91993a700aa4c81a0098
doc_id: 831867
cord_uid: 2s0w5fio

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the new coronavirus responsible for the coronavirus disease (COVID-19), characterized by acute respiratory distress syndrome and atypical pneumonia. In non-pregnant women, studies have shown that SARS-CoV-2 causes cardiac injury, which can result in myocardial inflammation and damage. Despite many studies investigating the extent of cardiac compromise in severely ill COVID-19 patients, little is known regarding its impact on pregnant women. Objective To illustrate the clinical, laboratory, radiological findings, and outcomes of COVID-19 pregnant patients who developed myocardial injury with ventricular dysfunction. Study Design We retrospectively reviewed the paper records of fifteen pregnant women with COVID-19, who developed myocardial injury on a single tertiary care hospital in the Dominican Republic. Patient's baseline characteristics, clinical picture, laboratory, and radiological findings were presented, and maternal and fetal outcomes were analyzed. Results Of 154 pregnant patients diagnosed with COVID-19 at our hospital during the study period, 15 (9.7%), developed myocardial injury. These patients' mean age and gestational age were 29.87 ± 5.83 and 32.31 ± 3.68, respectively. 66.7% of patients presented with shortness of breath and 16.3% with palpitations. All patients were admitted to the intensive care unit, and 86.6% needed intubation. Patients developed myocardial injury confirmed with highly elevated troponin (34.6 [14.4-55.5 ng/ml]), and pro-BNP concentrations (209 [184-246 pg/ml]). Additionally, all patients developed left ventricular dysfunction demonstrated by an echocardiogram with a mean left ventricular ejection fraction (LVEF) of 37.67 ± 6.4 %. Two patients that presented with palpitations passed away a few days after admission. Conclusion Our study showed COVID-19 induced myocardial injury and left ventricular dysfunction in pregnant women with a 13.3% mortality rate which was attributed to malignant arrhythmias.

J o u r n a l P r e -p r o o f Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) is the new coronavirus, responsible 116 for the highly infectious coronavirus disease , which was declared a global public health 117 emergency by the World Health Organization (WHO) on March 11, 2020 1-3 . As of August 9, 2020, 118 more than 19 million confirmed cases of COVID-19 had been reported globally, with 727,317 deaths 4 . 119

Emerging studies demonstrated the deleterious effect of SARS-CoV-2 on the cardiovascular (CV) 120 system such as myocardial injury which is associated with myocardial inflammation and damage 5 . 121

Almost 33% of non-pregnant COVID-19 patients admitted to the intensive care unit (ICU) develop 122 cardiac injury 6 . Despite many studies investigating the COVID-19 effect on adult patients' heart, little is 123 known regarding its impact on pregnant women. 124 125 Pregnancy leads to physiological, immunological, and mechanical changes that increase susceptibility to 126 infectious respiratory organisms predisposing to more severe illnesses 7 . Angiotensin-converting enzyme 127 2 (ACE-2) receptors are believed to be the door for SARS-CoV-2 entry into the host cells. Interestingly, 128 ACE-2 receptors expression is increased during pregnancy. SARS-CoV-2 downregulates ACE-2 129 receptors eliminating its cardioprotective effect and leading to increasing concentrations of tumor 130 necrotic factors alfa and inflammation, which could be the possible cause of myocardial dysfunction in 131 pregnant and non-pregnant COVID-19 patients 5 . In recent COVID-19 surveillance by the Center for 132

Disease Control (CDC), pregnant women were more likely to require hospitalization than non-pregnant 133 women (31.5% vs. 5.8%, respectively). 134 135 Moreover, pregnant women were significantly more likely to be admitted to ICU and receive 136 mechanical ventilation (adjusted relative risk =1.5, 95% confidence interval=1.2-1.8) compared to non-137 pregnant COVID-19 positive patients 7 . Intriguingly, there is a lack of studies investigating the effect of 138 COVID-19 on pregnant women's CV system. To our knowledge, only one study by Juusela et al., 139 showed the occurrence of cardiomyopathy in COVID-19 pregnant women, according to their results, out 140 of seven pregnant women with COVID-19 two developed cardiac dysfunction (28.6%; 95% CI, 8.2%-141 64.1%) with moderately reduced left ventricular ejection fraction of 40%-45% and hypokinesis 8 . 142

Therefore, it is crucial to understand the impact of COVID-19 on the heart of pregnant women. This 143 case series aims to describe the baseline, and clinical characteristics, laboratory, radiological findings, 144 and outcome of fifteen pregnant women admitted to a single tertiary care hospital with COVID-19 and 145 who developed myocardial injury. Investigating these cases would help provide a better understanding Patients were 29.87 ± 5.83 years-old and at 32.31 ± 3.68 weeks of gestation. All patients were 207 previously healthy and only 13.3% had prenatal bleeding (Table 1) . From fifteen patients, 66.6% 208 presented to the hospital with SOB, 13.3% with palpitations, 13.3% with DFM, and 6.6% with fatigue. 209

Patients were admitted to the hospital approximately 9.93 ± 3.13 days after the start of symptoms. All 210 patients had severe disease and were admitted to the ICU and 86.6% were intubated. (Table 2) . Almost 55% of patients had 216 abnormal ECG findings where 13.3% had irregular rhythms, 33.3% BBB, 40% ST depression, and 40% 217 T wave inversion. In terms of patients' chest x-rays, all patients had lung consolidation, and 6 (40%) 218 had ground-glass opacities. The CTI of patients were 0.5 ± 0.06. In terms of patients TTE, all patients 219 had abnormal findings were all presented with left ventricular dysfunction with a mean LVEF of 37.67 220 ± 6.4 and LV diffuse hypokinesis. Additionally, 20% had left atrial dilatation and 13% LV dilation. 221 222 J o u r n a l P r e -p r o o f

All patients were delivered by c-section were 60% were delivered prematurely. The mean gestational 224 age at delivery was 34.2 ± 4 weeks. From fifteen patients 13.3% died after delivery due to malignant 225 arrhythmias (ventricular tachycardia and torsade de point). One clinically unstable mother was delivered 226 at 23.3 weeks of pregnancy by an emergent c-section due to a significant decrease in fetal heart rate; the 227 child was delivered and was unresponsive with an APGAR score of 0 at 0 and 5 mints. No autopsy or 228 additional tests were performed to determine the cause of death (Table 3) . A great proportion of patients 229 had to deliver their babies prematurely (60%) due to their unstable clinical (unstable vitals, severe 230 hypoxemia arrhythmia) condition and fetal bradycardia. This was decided when the physician believed 231 that the continuation of pregnancy results in jeopardy of the mother and fetus's life. 232

From 14 infants, 6 (35.7%) of the infants had low birth weight (weight <2.5 Kg) and 1 (7.1%) had very 233 low birth weight (<1.5 Kg).8 (57%) of the infants had a reassuring APGAR score at 0 and 5 minutes, 3 234 (21.5%) had a moderately depressed APGAR score at 0 min and a reassuring score at 5 min and 3 235 (21.5%) had a moderately depressed score at 0 and 5 mins. Additionally, 5 (35.7%) infants were 236 admitted to the NICU (premature infants with low birth weight) and discharged later. injury with reduced LVEF, which ranged from 22-45% with a 37.67 ± 6.4 mean. All fifteen cases had 274 very high elevated troponin and BNP concentrations with or without ECG changes and were admitted to 275 the ICU. It is unknown if the incidence of cardiac injury in these patients is due to the direct effect of 276 SARS-CoV-2 virus or secondary to multiorgan failure due to overwhelming critical illness. Older 277 patients with COVID-19 and comorbidities are more likely to developed cardiac injury. Intriguingly, our 278 patients were young, previously healthy females with minimal CV risk factors; this makes a statement 279 regarding the impact of COVID-19 disease in the CV system. It can cause cardiac compromise, even in 280 the absence of previous CVD. It is worth mentioning that surprisingly, two studies showed that the 281 prevalence of acute myocardial injury in COVID-19 patients increased patients' mortality significantly 282 more than age, previous CVD, CV risk factors, and chronic pulmonary disease 6,14 . Therefore, it is 283 essential to identify cardiac injury in pregnant patients to avoid complications early in their disease 284 course. 285

Arrhythmia and sudden cardiac arrest are also common CV complications of COVID-19 patients 15 being the most common type 13 . This fact is consistent with our findings because 26.6% of patients had 291 sinus tachycardia, and 13.3% had atrial fibrillation. Unfortunately, the two patients that presented with 292 atrial fibrillation had an emergency c-section and passed away 3 and 6 days after hospitalization due to 293 torsade de pointes and sustained ventricular tachycardia. In our study, the new-onset atrial fibrillation in 294 patients with respiratory distress syndrome is associated with an increase in the 90-day mortality 16 Similarly, in a retrospective study of 72 COVID-19 patients who had echocardiography due to major 312 concern of acute cardiovascular event or due to hemodynamic instability, 34.7% had a reduced LVEF in 313 which 45.7% had an elevated troponin concentration and reduced LVEF 19. It is worth noting from 314 these patients, it was unknown who had pre-existing LV dysfunction. Both studies showed that the 315 prevalence of ventricular dysfunction in COVID-19 patients to be common which is consistent with our 316 study 18,19. However, when compared with our study, from fifteen patients with elevated cardiac 317 troponin concentrations 100% had reduced LVEF. This raises the question of an increased prevalence of 318 COVID-19 induced systolic dysfunction in pregnant women when compared to non-pregnant patients. J o u r n a l P r e -p r o o f 

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