key: cord-0773420-m5i37f67 authors: Jain, Sneha S.; Liu, Qi; Raikhelkar, Jayant; Fried, Justin; Elias, Pierre; Poterucha, Timothy J.; DeFilippis, Ersilia M.; Rosenblum, Hannah; Wang, Elizabeth Y.; Redfors, Bjorn; Clerkin, Kevin; Griffin, Jan M.; Wan, Elaine Y.; Abdalla, Marwah; Bello, Natalie A.; Hahn, Rebecca T.; Shimbo, Daichi; Weiner, Shepard D.; Kirtane, Ajay; Kodali, Susheel K.; Burkhoff, Daniel; Rabbani, LeRoy; Schwartz, Allan; Leon, Martin; Homma, Shunichi; DiTullio, Marco R.; Sayer, Gabriel; Uriel, Nir; Anstey, D. Edmund title: Indications and Findings on Transthoracic Echocardiogram in COVID-19 date: 2020-06-17 journal: J Am Soc Echocardiogr DOI: 10.1016/j.echo.2020.06.009 sha: d1453209a742664cfca86de49944a0b499d2cc90 doc_id: 773420 cord_uid: m5i37f67 ABSTRACT Background Despite growing evidence of cardiovascular complications associated with novel 2019 coronavirus disease (COVID-19), there is little data regarding the performance of transthoracic echocardiography (TTE) and spectrum of echocardiographic findings in this disease. Methods We performed a retrospective analysis of adult patients admitted to a quaternary care center in New York City between March 1st and April 3rd, 2020. Patients were included if they had a TTE performed during the hospitalization after a known positive diagnosis for COVID-19. Demographic and clinical data were obtained using chart abstraction from the electronic medical record. Results Of 749 patients, 72 (9.6%) had a TTE following a positive SARS-CoV-2 PCR test. The most common clinical indications for TTE were concern for a major acute cardiovascular event (45.8%) and hemodynamic instability (29.2%). While most patients had preserved biventricular function, 34.7% were found to have a left ventricular ejection fraction (LVEF) ≤ 50% and 13.9% had at least moderately reduced right ventricular function. Four patients had wall motion abnormalities suggestive of stress-induced cardiomyopathy. Using Spearman rank correlation there was an inverse relationship between high sensitivity Troponin T and LVEF (rho = -0.34, p=0.006). Among 20 patients with prior echocardiograms, only two (10%) patients had a new reduction in LVEF of more than 10%. Clinical management was changed in eight (24.2%) of individuals who had a TTE ordered for concern for acute major cardiovascular event; and three (14.3%) in whom TTE was ordered for hemodynamic evaluation. Conclusions This study describes the clinical indications for usage and diagnostic performance, as well as findings seen on TTE in hospitalized patients with COVID-19. In appropriately selected patients TTE can be an invaluable tool for guiding COVID-19 clinical management. Demographic and clinical data were obtained using chart abstraction from the electronic medical record. Results: Of 749 patients, 72 (9.6%) had a TTE following a positive SARS-CoV-2 PCR test. The most common clinical indications for TTE were concern for a major acute cardiovascular event (45.8%) and hemodynamic instability (29.2%). While most patients had preserved biventricular function, 34.7% were found to have a left ventricular ejection fraction (LVEF) ≤ 50% and 13.9% had at least moderately reduced right ventricular function. Four patients had wall motion abnormalities suggestive of stress-induced cardiomyopathy. Using Spearman rank correlation there was an inverse relationship between high sensitivity Troponin T and LVEF (rho = -0.34, p=0.006). Among 20 patients with prior echocardiograms, only two (10%) patients had a new reduction in LVEF of more than 10%. Clinical management was changed in eight (24.2%) of individuals who had a TTE ordered for concern for acute major cardiovascular event; and three (14. 3%) in whom TTE was ordered for hemodynamic evaluation. Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). 2 A growing body of literature has highlighted the cardiovascular manifestations of COVID-19 and its impact on morbidity and mortality. [3] [4] [5] Echocardiography is a commonly used non-invasive imaging tool for assessment of cardiac pathology. However, COVID-19 places constraints on the utilization of echocardiography given the risk of exposure to personnel performing the study. In accordance with recommendations from the American Society of Echocardiography (ASE) 6 This study was conducted with approval from the NewYork-Presbyterian Columbia University Irving Medical Center Institutional Review Board. Patients older than 18 years of age admitted to Columbia University Irving Medical Center and New York-Presbyterian Allen Hospital and who tested positive for SARS-CoV-2 using a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay were screened to identify if they had a TTE during their admission from March 1 st , 2020 to April 3 rd , 2020 after a positive for SARS-CoV-2 RT-PCR test, and were included in this study. Data were obtained using both automated and manual chart abstraction from the electronic medical record. Abstracted data included demographics, comorbidities, presenting chief complaints, laboratory findings, echocardiogram order information, and clinical outcomes including endotracheal intubation and death. Comorbidities were derived from documentation upon hospital admission and included the following: hypertension, diabetes, obesity (defined as body mass index ≥ 30 kg/m 2 ), coronary artery disease, pulmonary disease (including asthma, chronic obstructive pulmonary disease, interstitial lung disease, or any primary lung disease that required home oxygen therapy), stage 3-5 chronic kidney disease by glomerular filtration rate using the Modification of Diet in Renal Disease Study equation, heart failure with a left ventricular ejection fraction (EF) ≤ 50%, heart failure with preserved EF, active cancer (defined as metastatic cancer, cancer that required treatment within the last 6 months, or cancer undergoing active observation), or history of cancer that did not meet the active cancer definition. Each chart was reviewed to determine the indication for ordering a TTE and were grouped into one of three categories: (1) hemodynamic assessment (volume status and evaluation of shock), (2) concern for a major acute cardiovascular event (rising cardiac biomarkers, acute coronary syndrome, myocarditis, pulmonary embolism), or (3) other. Each patient chart was reviewed following TTE to assess for any changes in clinical management. Laboratory values of high sensitivity troponin T (hs-cTnT) and N-terminal-proB-type natriuretic peptide (NT-proBNP) were manually abstracted from the electronic medical and the closest value prior to TTE was used for the analysis. We defined elevated hs-cTnT (>22 ng/L) and NT-proBNP (>1,800 pg/mL) by values that were greater than the 99 th percentile. Patients underwent TTE using Affiniti and EPIQ echocardiography systems (Phillips North America Corporation, Andover, MA). An abbreviated echocardiography protocol was developed using 2-dimensional and Doppler imaging to limit exposure to sonographers (Supplemental Table 1 ). In accordance with recommendations from ASE 6 and EACVI, 7 the use of echocardiography was limited in patients with confirmed or suspected COVID-19 to situations where the findings were expected to provide clinical benefit. Clinical appropriateness of echocardiograms was assessed on a case-by-case basis by an attending cardiologist after chart review and discussion with the clinical care team. Sonographers were asked to follow institutional protocol surrounding personal protective equipment (PPE) and ultrasound cleaning between cases, and were trained on proper donning and doffing of surgical face mask, cover gowns, and eye protection including face shields or goggles. Studies were independently analyzed by one of two board certified echocardiographers (DEA and QL) who were blinded to patient data. Echocardiographic study quality was evaluated on a subjective scale of adequate, mildly limited, moderately limited, severely limited, and non-diagnostic. For an adequate quality study, qualitative and quantitative parameters were evaluable on every image. Mildly limited denoted that some quantitative parameters could not be accurately assessed. In a moderately limited study, quantitative parameters were less reliable, but qualitative assessment could be performed. In a severely limited study, some qualitative parameters could not be reliably evaluated, but major parameters such as left ventricular function could still be assessed. A non-diagnostic study indicates that no diagnostic images could be obtained. LV measurements were made in the parasternal long-axis views in accordance with the 2015 ASE and EACVI guidelines on chamber quantification. 8 Consistent with these guidelines, the normal range of LV dimensions by sex were defined as the mean ± 1.96 standard deviations (SD) reported by the ASE and EACVI and subsequent grades of abnormality (mild, moderate and severe) were defined by incremental addition of 1 SD such that severely abnormal was a value greater than the mean + 4 SDs. LV ejection fraction (LVEF) was assessed by visual estimation and modified Simpson's biplane method when LVEF appeared abnormal and image quality allowed for accurate quantitation. RV size was assessed using RV basal and mid dimensions when technically feasible, but visual estimation if image quality was not adequate for accurate measurement. Right ventricular (RV) function was assessed semi-quantitatively and valvular regurgitation was qualitatively assessed. Pulmonary artery systolic pressure (PASP) was calculated based on an estimate of RV systolic pressure using the tricuspid regurgitant (TR) jet, 9 and an estimate of mean right atrial pressure using the inferior vena cava size and collapsibility in non-intubated patients. 10 The institutional echo database was also searched for prior studies on each patient, and the most recent prior study was analyzed by one of the two study echocardiographers for direct comparison. The clinical outcomes of death and mechanical ventilation were assessed by chart review for thirty days after TTE. Descriptive statistics only were reported for demographics, comorbidities, laboratory and echocardiographic findings, and clinical outcomes. For laboratory and echocardiographic measurements, continuous variables were expressed as mean ± SD. Categorical variables were summarized as counts and percentages. The laboratory values of hs-cTnT and NT-proBNP were log-transformed before analyses to ensure normal distribution. Correlations between hs-cTnT and NT-proBNP and their individual correlations with LVEF were explored using Spearman rank correlation with a qualitative interpretation of the strength of the relationship. 11 Statistical analyses were performed using R (version 4.0.0). During the study period, 749 patients were admitted and found to be COVID-19 positive by SARS-CoV-2 PCR testing during the study period. Of these patients, 72 (9.6%) had a formal TTE following a positive SARS-CoV-2 test and were included in the present analysis. Baseline characteristics are shown in Table 1 The most common clinical indications for ordering a TTE included hemodynamic assessment (29.2%) and concern for a major acute cardiovascular event (rising cardiac biomarkers, pulmonary embolism, acute coronary syndrome, heart failure, or myocarditis; 45.8%). The remaining indications included known history of cardiac disease, evaluation for endocarditis, and evaluation for cardioembolic source of stroke (Figure 1 ). On average (SD), studies were performed in 6.7 (3.4) minutes and included 39.7 (17.5) clips. 29 (40.3%) studies were adequate or mildly limited in quality, 29 (40.3%) were moderately limited, 10 (13.9%) were severely limited, and 4 (5.6%) were non-diagnostic. Of the 40 intubated patients, 12 studies (30%) were adequate or mildly limited, 16 (40%) were moderately limited, 9 (22.5%) were severely limited, and 3 (7.5%) were non-diagnostic. Diastolic and systolic LV measurements could not be measured in 10 (13.9%) and 24 (33.3%) of patients respectively (Supplemental Table 2 ). LV diastolic and systolic linear dimensions were increased in 6 (8.3%) and 12 (16.7%) patients respectively. LV global and regional function are listed in (Table 2) . LVEF was evaluable in 68 (94.4%) patients. Of these, 59 (87%) were assessed by visual estimation and 9 (13%) were assessed using modified Simpson's biplane method. The majority (59.7%) of the cohort had a LVEF > 50% ( Table 2) Table 3 ). Supplemental Table 4 . RV size was normal or borderline increased in 50 (69.4%) patients ( Table 3) . Nine (12.5%) patients had mildly increased RV size, and only two patients had moderately or severely increased RV size. RV function was normal in 34 (47.2%), mildly decreased in 19 (26.4%), moderately decreased in seven (9.7%), and severely decreased in three (4.2%) patients ( Table 3) . Moderate or greater valve regurgitation was noted in seven patients (1 moderate aortic insufficiency, 2 moderate or severe mitral regurgitation, 4 moderate or severe tricuspid regurgitation). An accurate maximal TR velocity was able to be evaluated in 26 (36.1%) patients, while 46 (63.9%) could not be evaluated due to poor data quality or incomplete TR envelope. Sixty-nine (95.8%) of 72 patients had a hs-cTnT measured prior to a TTE and 48 patients had an NT-proBNP prior to a TTE ( Table 4 ). There was a weak inverse relationship between hs-cTnT and LVEF (rho= -0.34, p=0.006). There was a trend towards a weak inverse relationship between NT-proBNP and LVEF (rho= -0.29, p=0.056), which did not meet statistical significance (Supplemental Figure 1) . Twenty individuals in this cohort had a prior TTE available for review. On average, the prior echocardiograms were performed in 18 minutes and included 91.7 clips. On prior TTE, seven patients had a reduced LVEF of <50% of which all seven also had a reduced LVEF <50% on the current TTE. When comparing the prior to the current echocardiograms, two patients had a reduction in LVEF greater than 10%. Of these, one patient had previously normal LVEF and new wall motion abnormalities consistent with stress-induced cardiomyopathy, while the other had worsened global LV function of a previously diagnosed cardiomyopathy. One patient had an increase in RV size from the prior study. Six patients had a reduction in RV function, with five decreasing from normal to mildly reduced and one decreasing from mildly to moderately reduced. Three of the eight patients with focal wall motion abnormality had prior TTEs. Of those patients, two had pre-existing wall motion abnormality. Abnormal findings on TTE directly impacted clinician decision making in 12 (16.7%) patients. Clinical management was changed in eight (24.2%) of individuals who had a TTE ordered for concern for acute major cardiovascular event; and three (14.3%) in whom TTE was ordered for hemodynamic evaluation. Four patients had findings consistent with pulmonary embolism and were started on anticoagulation. The remaining eight patients had newly discovered LV systolic dysfunction, and four were critically ill. Two patients were started on inotropic support and one patient who was already on veno-venous extracorporeal membrane oxygenation had an arterial limb added. One patient was transferred from an affiliated community hospital to the main campus for evaluation for extracorporeal membrane oxygenation; this patient was declined for extracorporeal membrane oxygenation by a multidisciplinary heart team but eventually was weaned off vasoactive agents. Three patients were diagnosed with systolic heart failure and were started on therapies or arranged to have outpatient cardiology follow-up. Finally, one patient was planned for a trial of diuresis, but given poor prognosis related to cardiomyopathy and other comorbidities, the patient was transitioned to comfort focused care. During the 30-day follow-up period after TTE, 4 patients who were previously not intubated required intubation and 24 (33.3%) died (Supplemental Table 6 ). In the setting of the global COVID-19 pandemic, the utilization and performance of echocardiography has changed significantly, as the risk of transmission to sonographers and other providers became an important concern. As such, our lab has implemented rigorous screening measures and changes to the standard echocardiography protocol consistent with a recent statement from the ASE. 6 We found that these changes translated to a decrease in the number of images acquired per study and the total acquisition time per patient. While many studies did have some limitations in data quality, very few studies were severely limited or nondiagnostic. Given the complexity and severity of the clinical course of hospitalized patients with COVID-19, many studies were performed in the critical care setting where patients are often unable to cooperate with exam maneuvers and there are many physical impediments to optimal image acquisition. Despite these challenges, our experience shows that the utility of echocardiography remains high and interpretable images could be obtained efficiently in the majority of patients. Multiple cardiac manifestations of COVID-19 have been described in case reports, including fulminant myocarditis, acute RV dysfunction, and cardiac tamponade, but the spectrum and incidence of cardiac disease in COVID-19 has not been well elucidated. 3, 4, 12 In our cohort, the majority of patients were found to have preserved biventricular systolic function. However, significant LV and RV systolic dysfunction was found in a subset of patients and must be interpreted within the clinical context of a patient with COVID-19. We do not know how many of these reduced LVEFs were pre-existing and results should be interpreted with caution. Little is known about the pathologic effects of COVID-19 on the myocardium. In an analysis by Li. et al., patients with the phylogenetically similar severe acute respiratory syndrome coronavirus (SARS-CoV) had subclinical diastolic dysfunction without significant systolic impairment. 13 In contrast, LV systolic dysfunction was prevalent in our cohort, raising concern for potential direct viralmediated cardiotoxicity versus systemic inflammation leading to depression of myocardial function. Four patients also had apical hypokinesis with basal sparing consistent with stressinduced cardiomyopathy, suggesting another possible etiology for acute LV systolic dysfunction. In our cohort, RV systolic dysfunction was more common than LV systolic dysfunction. The etiology of this RV dysfunction is unclear. 56% of the cohort was intubated at the time of their echocardiogram. RV dysfunction is a known complication of hypoxemic injury including acute respiratory distress syndrome [14] [15] [16] [17] and can be a hemodynamically significant and deleterious consequence of mechanical ventilation. 18, 19 Further, hemodynamic instability and RV dysfunction in the context of acute respiratory distress syndrome is thought to correlate with mortality. 17, 20 However, the abnormalities in RV size and function in this critically ill population may also raise concern for pulmonary thromboembolism which is a prevalent complication of COVID-19. 21 Previous studies have linked an elevated d-dimer at admission to a higher mortality in patients with COVID-19 22 with multiple case reports of pulmonary emboli. 23 Klok et al recently evaluated the thrombotic complications of 184 intensive care unit patients and found that the composite incidence of symptomatic acute pulmonary embolism, deep-vein thrombosis, ischemic stroke, myocardial infacrtion or systemic arterial embolism in COVID-19 patients was 31%, with 25/31 (81%) from pulmonary embolism. 21 The primary reasons for ordering a TTE were to better understand a patient's hemodynamics or concern for an acute cardiac event as suggested by a rise in hs-cTnT or NT-proBNP, such as a pulmonary embolism, myocarditis, or myocardial infarction. Abnormal biomarkers were a common indication for TTE in our cohort. Among patients with an elevated hs-cTnT, 46% were found to have a reduced LVEF on TTE. Guo et al recently described the pattern of acute increase in both hs-cTnT and NT-proBNP in patients with impending cardiac death. 24 Given these findings it may be reasonable to use elevation in cardiac biomarkers such as hs-cTnT and NT-proBNP as a screening mechanism for patients more likely to have a clinically meaningful abnormality on TTE. A change in management occurred for 12 (16.7%) patients as a direct result of TTE findings. Most notably, anticoagulation was initiated in a small subset of patients for presumed pulmonary embolism because of the TTE findings. We postulate that additional changes in clinical management may have been influenced by TTE, such as giving more fluid for the management of shock in a patient found to have normal LV function. In the clinical management of hemodynamically unstable patients, many echocardiographic findings may be of high clinical utility. In our cohort, biventricular systolic function could be assessed in most patients, and severe LV or RV dysfunction was seen in some critically ill patients. Other hemodynamic parameters, which may guide clinical management, include inferior vena cava size and collapsibility, and PASP estimation. 10 In our cohort, PASP could not be estimated in the majority of patients due to poor data quality or incomplete TR envelope. This highlights one of the limitations of an abbreviated protocol, as 43 patients (59.7%) had less than mild TR, and in the absence of significant TR, more thorough imaging from multiple views is often required to obtain a complete TR envelope. Communication between echocardiographers and clinical providers becomes even more important in these patients, as protocols can be better tailored to answer specific clinical questions. In this regard, handheld echocardiography may take on increased importance during the COVID-19 pandemic, particularly for rapid assessment of the inferior vena cava as a marker of volume status. This study must be interpreted with the context of the study limitations. First, our study may be subject to referral bias, as TTEs may have been ordered in more severely ill patients and requests were further screened by a cardiologist to exclude patients in whom a TTE was not indicated. Second, this a retrospective case-series of patients admitted to a hospital with no concurrent control group. Clinical history was abstracted from the electronic medical record and was not collected prospectively as part of a research protocol. Third, while this is a multi-site study, it includes a modest-size cohort in two hospitals staffed by the same medicine and cardiology departments. Whether similar findings would be observed in a larger, multi-center study is an important area of future investigation. Fourth, as described in the methods TTEs performed were abbreviated in keeping with ASE and EACVI guidelines. As a result of this approach, some measures such as diastolic function and strain were not performed. Fifth, the majority of patients did not have prior TTE which limits the ability to determine the acuity of the observed pathologies and if they preceded the diagnosis of COVID-19. Finally, positive end expiratory pressure was not recorded at the time of the echo and therefore was unable to be included in this analysis. Importantly, the range of normal LV dimensions are based on reported the mean ± 1.96 SD reported by the ASE and EACVI 8 but the degree of abnormality is based on increasing SD's above the 95% confidence limit for the measure and may require further validation. This study summarized the various echocardiographic findings of hospitalized patients with COVID-19 and suggest that an echocardiogram may be a clinically useful tool for guiding management in appropriately selected patients. Elevated cardiac biomarkers including hs-cTnT and NT-proBNP may be useful tool as part of the clinical assessment to determine which patients with COVID-19 are likely to have abnormal findings on TTE. KC receives support through NIH Grant K23 HL148528. MA receives support through 18AMFDP34380732 from the American Heart Association and from the NIH/NHLBI (K23 HL141682-01A1 and R01HL146636-01A1). NAB receives support through NIH Grant K23 HL136853. Unable to Assess 3 (11.1%) 0 (0%) 1 (4.2%) Abbreviations: hs-cTnT: High sensitivity troponin T, NT-proBNP: N-terminal-pro hormone B-type natriuretic peptide, TTE: Transthoracic echocardiogram Normal hs-cTnT defined as ≤ 22 ng/L Elevated hs-cTnT defined as > 22 ng/L Normal NT-proBNP defined as < 1800 pg/mL Elevated NT-proBNP defined as ≥ 1800 pg/mL Indications for performing a transthoracic echocardiogram on patients with novel 2019 coronavirus disease. An interactive web-based dashboard to track COVID-19 in real time Critically Ill Patients in the Seattle Region -Case Series COVID-19 and Cardiovascular Disease Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic The Variety of Cardiovascular Presentations of COVID-19 Recommendations for Echocardiography Laboratories Participating in Cardiac Point of Care Cardiac Ultrasound (POCUS) and Critical Care Echocardiography Training: Report from the American Society of Echocardiography COVID-19 pandemic and cardiac imaging: EACVI recommendations on precautions, indications, prioritization, and protection for patients and healthcare personnel Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography Guidelines for the use of echocardiography as a monitor for therapeutic intervention in adults: a report from the American Society of Echocardiography Biostatistics primer: part 2 Left ventricular performance in patients with severe acute respiratory syndrome: a 30-day echocardiographic follow-up study The Right Ventricle in ARDS Vascular obstruction causes pulmonary hypertension in severe acute respiratory failure Pulmonary hypertension in severe acute respiratory failure Diagnostic workup, etiologies and management of acute right ventricle failure : A state-of-the-art paper Diagnostic accuracy and therapeutic impact of transthoracic and transesophageal echocardiography in mechanically ventilated patients in the ICU A decade of progress in critical care echocardiography: a narrative review Acute respiratory distress syndrome: the heart side of the moon Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Acute pulmonary embolism and COVID-19 pneumonia: a random association? Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19) TJP owns stock in Abbott Laboratories, Abvie, Inc., Edwards Lifesciences, and Baxter International. RTH reports speaker fees from Baylis Medical, Edwards Lifescience and Medtronic; consulting for Abbott Structural, Edwards Lifesciences, Medtronic, Navigate, and Philips Healthcare; non-financial support from 3mensio; Equity with Navigate; and is the Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, for which she receives no direct industry compensation. AK reports Institutional funding to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, Philips, ReCor Medical. Personal: CME program honoraria and travel/meal reimbursements only.