key: cord-281870-ax5s2i6t
authors: Goerlich, Erin; Gilotra, Nisha A.; Minhas, Anum S.; Bavaro, Nicole; Hays, Allison G.; Cingolani, Oscar H.
title: Prominent Longitudinal Strain Reduction of Basal Left Ventricular Segments in Patients with COVID-19
date: 2020-09-28
journal: J Card Fail
DOI: 10.1016/j.cardfail.2020.09.469
sha: 
doc_id: 281870
cord_uid: ax5s2i6t

BACKGROUND: COVID-19 has been associated with overt and subclinical myocardial dysfunction. We observed a recurring pattern of reduced basal left ventricular (LV) longitudinal strain (LS) on speckle-tracking echocardiography (STE) in hospitalized COVID-19 patients and subsequently aimed to identify characteristics of affected patients. We hypothesized that COVID-19 patients with reduced basal LV strain would demonstrate elevated cardiac biomarkers. METHODS: 81 consecutive COVID-19 patients underwent STE. Those with poor quality STE (n=2) or known LV ejection fraction<50% (n=4) were excluded. Patients with absolute value basal LS<13.9% (2SD below normal) were designated as cases (n=39); those with basal LS≥13.9% as controls (n=36). Demographics and clinical variables were compared. RESULTS: Of 75 included patients (mean age 62±14 years, 41% women), 52% had reduced basal strain. Cases had higher BMI (median[IQR]) (34.1[26.5-37.9]kg/m(2) vs. 26.9[24.8-30.0]kg/m(2), p=0.009), and greater proportions of Black (74% vs. 36%, p=0.0009), hypertensive (79% vs. 56%, p=0.026) and diabetic patients (44% vs. 19%, p=0.025) compared to controls. Troponin and NT-proBNP levels trended higher in cases but were not significantly different. CONCLUSIONS AND RELEVANCE: Reduced basal LV strain is common in COVID-19 patients. Patients with hypertension, diabetes, obesity, and Black race were more likely to have reduced basal strain. Further investigation into the significance of this strain pattern is warranted.

Coronavirus Disease 2019 resulting from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic with high morbidity and mortality. While the respiratory system sees the major impact of the illness, increasing reports describe important cardiac manifestations, which are in turn associated with poor outcomes. 1-4 Various forms of myocardial injury, defined by elevated cardiac biomarkers and/or abnormalities on transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) have been reported. 2, 5-9 TTE can be particularly useful in the inpatient setting to quickly and inexpensively evaluate regional myocardial injury, however due to the infectious risk to medical staff, routine echocardiography for all COVID-19 patients should be avoided. 10 A technique easily combined with standard echocardiographic measurements is 2-dimensional speckle-tracking echocardiography (STE), which tracks unique speckle pathways during the cardiac cycle to determine myocardial deformation/strain. Global longitudinal strain (GLS) has been shown to be more sensitive in detecting left ventricular (LV) dysfunction compared to LV ejection fraction (LVEF). 11 Regional strain can be analyzed based on the American Heart Association (AHA) 17-segment model of the LV, represented as a "bull's-eye" polar map with the LV apex in the center and each segment color-coded according to level of strain ( Figure) .

Segmental longitudinal strain (LS) patterns can be helpful in identifying cardiac diseases when a characteristic abnormality is seen in conjunction with clinical data, such as the pathognomonic apical-sparing strain reduction seen in cardiac amyloidosis. 12 A recurring pattern of reduced basal LV LS on STE was observed in hospitalized COVID-19 patients (Figure) . This study aimed to characterize the COVID-19 patient population with this strain pattern. We hypothesized that cardiac biomarker levels would be elevated in patients with reduced basal LS. Images were analyzed by two independent reviewers on a dedicated workstation using EchoPAC software (version 202, GE ultrasound). Within this manuscript, strain is referred to in absolute value.

Hospitalized COVID-19 patients who underwent STE during admission were assessed for regional strain. Patients with a history of LVEF<50%, arrhythmia at time of TTE, or insufficient quality to ascertain regional strain were excluded. Polar maps based on the AHA 17-segment model were analyzed for LS at basal, mid, and apical levels. Mean basal LS in healthy patients has been reported as -18.3%±2.2; therefore, patients with an average absolute value basal LS<13.9% (2 SD from normal) were designated as cases. 13 Otherwise, patients were considered controls. Clinical and demographic variables were collected from the electronic medical record and de-identified. Normality was assessed with Shapiro-Wilk testing.

Comparisons between groups were performed using Welch's t-test for normally distributed continuous variables that passed Levene's test for homogeneity of variance, Mann-Whitney U test for skewed continuous variables or those with unequal variance, and χ 2 or Fisher's exact test, as appropriate, for categorical variables. Laboratory data were recorded at peak level.

Analyses were performed using GraphPad Prism v.8.4.2. A p-value <0.05 was considered statistically significant.

In total, 81 COVID-19 patients underwent STE, and 75 were included in the analysis; 2 were excluded for poor quality, and 4 were excluded for prior LVEF<50%. Mean age was 61.9±13.5 years, and 41% were women. There were high overall incidences of ICU admission (73%), mechanical ventilation (61%), shock (47%), and death (17%). 52% of patients had reduced basal strain on STE (basal LS 10.0±2.9% vs. 16.9±2.3%, p<0.001). LVEF was similar between groups, however GLS was significantly lower in cases compared to controls (13.9±4.1% vs. 15 These findings support studies showing LV GLS as a more sensitive marker of early myocardial dysfunction than LVEF in a variety of etiologies. 11 Additionally, this suggests that bedside STE provides important information regarding cardiac involvement early in the course of COVID-19.

Complementing our findings, a recently published study describing reduced basal segmental LV strain in over half of evaluated COVID-19 patients has suggested that this is may be an early marker of myocardial involvement. 9 Abnormalities in RV strain and LV GLS have also been reported and indicate subclinical myocardial injury. 5, 6 Importantly, CMR in a significant proportion of recovered COVID-19 patients revealed fibrosis and edema predominantly in the basal and mid LV segments, corresponding with our STE findings. 8 Case reports and series of patients with various forms of myocarditis, including influenza myocarditis, have described a similar pattern of reduced basal strain on STE. 16, 17 Abnormal basal LS has also been seen in infiltrative cardiomyopathies including Anderson-Fabry disease (AFD). 18 One study of CMR in AFD patients suggested that basal inferolateral segments represent the area of basal LV with the greatest mobility throughout the cardiac cycle and thus may be more susceptible to junctional stresses. 19 These prior findings, along with our current work, raise the possibility that this basal injury pattern reflects susceptibility of certain myocardial regions to inflammatory or systemic stressors rather than a geographic predilection specific to SARS-CoV-2. Further supporting this theory are studies showing apical-sparing LV dysfunction in patients with acute brain hemorrhage. 20, 21 The associated catecholamine surge in these clinical scenarios may also contribute to cardiac injury in COVID-19.

Another plausible hypothesis, more specific to COVID-19, involves the viral receptor, angiotensin-converting enzyme 2 (ACE2). This membrane-bound enzyme is responsible for production of Angiotensin (1-7) , leading to well-described anti-inflammatory and anti-thrombotic effects. 22 ACE2 is highly expressed in fat, and epicardial adipose tissue (EAT) is more prominent in the atrioventricular groove and lateral LV wall, closer to the basal segments. 23 Loss of ACE2 has been shown to result in heart failure with preserved ejection fraction, mediated in part by EAT inflammation. Angiotensin (1-7) reduces obesity-associated cardiac dysfunction predominantly via its role in adiponectin expression and attenuation of EAT inflammation. 22 Thus, SARS-CoV-2 binding of ACE2 may occur more prominently in areas of high EAT, such as the basal LV, and cause subclinical dysfunction via inflammatory downstream effects, perhaps more readily in overweight/obese patients.

Our study also presents some limitations. The modest sample size may lead to type II errors in cardiac biomarker and clinical comparisons. Furthermore, the proportion of women was higher in the low basal strain group, which is unexpected considering that men are more likely to contract COVID-19, and suffer worse outcomes. 24 This sex difference could also blunt differences in biomarkers and outcomes. While the reduced basal LV strain was found during 

In summary, we report a pattern of reduced LV basal strain seen in over half of studied COVID-19 patients and occurring more frequently in patients with high-risk cardiovascular comorbidities and Black race. Although this study was not powered to detect differences in hard clinical outcomes such as death, it is known that Black patients and those with obesity, hypertension, and diabetes have worse overall outcomes with COVID-19. This strain pattern often occurs despite preserved LVEF and may herald early subclinical myocardial injury. Further studies in larger COVID-19 cohorts are warranted to determine prognostic significance. 

Additional echocardiographic variables representing LV structure, diastolic function, and right ventricular function were not different between groups (Table)

Cases had higher body mass index (BMI; , p=0.009), and prevalence of hypertension (79% vs. 56%, p=0.026), and diabetes mellitus (44% vs. 19%, p=0.025). There was a higher proportion of Black patients among cases

Levels of troponin I and N-terminal pro-brain natriuretic peptide trended higher

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