key: cord-0899461-zmhugmbq authors: Italia, Leonardo; Ingallina, Giacomo; Napolano, Antonio; Boccellino, Antonio; Belli, Martina; Cannata, Francesco; Rolando, Marco; Ancona, Francesco; Melillo, Francesco; Stella, Stefano; Ripa, Marco; Scarpellini, Paolo; Tresoldi, Moreno; Ortalda, Alessandro; Righetti, Beatrice; De Cobelli, Francesco; Esposito, Antonio; Ciceri, Fabio; Castagna, Antonella; Rovere, Patrizia Querini; Fragasso, Gabriele; Agricola, Eustachio title: Subclinical myocardial dysfunction in patients recovered from COVID‐19 date: 2021-10-21 journal: Echocardiography DOI: 10.1111/echo.15215 sha: cbf6e7b279ec250792613551220c6243ffc26c46 doc_id: 899461 cord_uid: zmhugmbq BACKGROUND: Myocardial injury (MI) can be detected during the acute phase of Coronavirus disease 19 (COVID‐19) and is associated with a dismal prognosis. Recent imaging studies described the persistence of cardiac abnormalities after the recovery. The aim of the study was to investigate the spectrum of cardiac abnormalities at mid‐term follow‐up in patients recovered from COVID‐19 using clinical assessment, laboratory tests, and imaging evaluation with comprehensive echocardiography. METHODS: This is an observational, cross‐sectional study assessing an unselected cohort of consecutive patients recovered from COVID‐19. MI was defined by elevated plasma levels of high sensitive troponin T (hsTnT). At the follow‐up, a complete examination including echocardiography was performed. RESULTS: The 123 patients included were divided into two groups according to the presence of MI during hospitalization: group A (without MI) and group B (with MI). After a median of 85 days, group B patients were more frequently symptomatic for dyspnea and had significantly higher values of hsTnT and N‐Terminal prohormone of Brain Natriuretic Peptide (NT‐proBNP), compared to Group A. No differences between the two groups in left nor right ventricle dimension and ejection fraction were found. However, in group B a significant reduction of mean left ventricle global longitudinal strain was observed (‐15.7±.7 vs ‐18.1± .3 in group A, p < 0.001), together with higher frequency of impaired diastolic function and higher values of pulmonary pressure. CONCLUSIONS: In patients recovered from COVID‐19, echocardiography with speckle‐tracking analysis may be an useful imaging tool to identify subclinical myocardial dysfunction and potentially guide management strategies. This is an observational, cross-sectional study conducted at a large ter- Patients affected by these conditions were excluded because these disorders can cause an increase of troponin serum levels that is potentially unrelated to COVID-19 infection. 18 Clinical, laboratory and biological data on all hospitalized patients were collected and included an electrocardiogram (ECG), high sensitivity troponin T (hsTnT), hematocrit, serum creatinine, C-reactive protein levels N-Terminal prohormone of Brain Natriuretic Peptide (NT-proBNP) serum levels. Myocardial injury was defined by plasma levels of hsTnT greater than 13.9 ng/L, representing the 99th upper reference limit of the Cobas 8000 assay (Roche, Switzerland). 19 ACS was excluded evaluating clinical symptoms, ECG and serum troponin values, according to the current guidelines. 20 Following an appropriate period after the recovery, a complete examination including medical history, physical examination and a comprehensive echocardiography was performed. Moreover, blood test including hsTnT, hematocrit, C-reactive protein levels, and NT-proBNP serum levels were collected. Patients and/or the public were not involved in the design, conduct, reporting, or dissemination plans of this research. Categorical data are showed as numbers and percentages; continuous variables as means ± standard deviation or medians with inter-quartile ranges (IQRs) when appropriate. An unselected cohort of 140 consecutive patients who recovered from COVID-19 infection was evaluated; 17 patients met the exclusion criteria, therefore a total of 123 patients were included in the final analysis ( Figure 1 ). Baseline characteristics of the overall population and the two groups are provided in Table 1 . In the overall population, 31 patients (24%) underwent noninvasive ventilation with positive airway pressure and one patient required invasive mechanical ventilation. In addition to respiratory support, patients received antiviral (51%), hydroxychloroquine (57%), tocilizumab (4%), antibiotic (56%), heparin (52%), and steroid (14%) therapy. All patients were in sinus rhythm at the time of the admission; 42% of them presented nonspecific ventricular repolarization Laboratory exams of group B (MI+) showed significantly higher values of C-Reactive protein, NT-proBNP, creatinine and white blood cells. The values are expressed as number of patients. In the overall population, 16 patients reported dyspnea even during less-than-ordinary activity, for example, walking short distances (New York Heart Association class III). Group B patients (MI+) were more frequently symptomatic for dyspnea ( Table 2 and Figure 2 ). All the echocardiographic measurements are reported in Table 3 . No differences between the two groups in 3D left and right ventricle volumes and ejection fraction were found (Table 3 (Table 3 and Figure 2 ). HsTnT values were persistently elevated at follow-up examination in 13 patients (11% The values are expressed as mean ± standard deviation, median (inter-quartile ranges) or number (percentages) as appropriate. Intra-observer agreement was excellent for global longitudinal 2D strain (Table 5 ). Our study represents an attempt to systematically characterize the spectrum of cardiac abnormalities at mid-term follow-up among hospitalized patients recovered from COVID-19. The main findings of our study are: (1) Subclinical MI during the acute phase of the infection has emerged as a relatively frequent complication with dismal prognostic consequences. 6 Clinical presentation of the chronic myocarditis with other etiology is highly variable and the prognosis might be good for the majority of the patients; however, it can be impaired if the healing of myocarditis is incomplete 24, 25 and patients may subsequently develop heart failure. 24, 26 In this setting, the early identification of unhealed myocarditis could be helpful to guide the beginning of cardioprotective therapy. GLS has been previously suggested as an alternative to CMR in the diagnosis of chronic myocardial inflammatory disease. 27, 28 LV GLS is recommended for clinical use to detect slight MI in heart failure, chemotherapy-related cardiotoxicity, and infiltrative diseases. 29, 30 In addition, strain imaging with regional speckle-tracking assessment has been proposed as a potential surrogate for CMR late gadolinium enhancement (LGE) imaging. 31 Finally an abnormal LV GLS by TTE has demonstrated an adequate diagnostic performance, compared to CMR, to detect chronic myocarditis in patients with LV normal EF with 82% sensitivity, 70% specificity, and 76% accuracy. 28 In the setting of COVID-19, LV GLS proved to be an independent predictor of in-hospital mortality. 32 Although the long-term effects of LV GLS decrease cannot be determined in COVID- 19, it has been related to worse outcomes in chronic myocarditis of other etiologies. 33, 34 Moreover, patients with MI presented at follow-up higher frequency of impaired left ventricular diastolic function with larger left atrial volumes and higher values of pulmonary artery pressure. Those data are concerning, since in the scenario of chronic myocardial inflammatory process, the evolution to heart failure with preserved EF has been already described. 24 The data of the present study suggest that: (1) Our study has some potential limitations. First, there was no assessment of echocardiographic data during hospitalization. Second, we did not include CMR and cardiac computed tomography imaging data. Moreover, NYHA class assessment in patients with previous COVID-19 pneumonia may be affected by a lung damage. The results of this study suggest that patients with MI during the acute phase of COVID-19 may present mid-term subclinical myocardial dysfunction that can be assessed by LV GLS analysis and may show higher grades of diastolic impairment. Long-term follow-up is needed in order to evaluate the prognostic and clinical implications of these findings. In patients recovered from COVID-19, TTE with speckle-tracking analysis could be a useful imaging tool to identify patients with subclinical MI and potentially guide management strategies. Francesco Cannata MD https://orcid.org/0000-0002-5842-5293 Eustachio Agricola MD https://orcid.org/0000-0002-4834-2187 Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19) Coronavirus and cardiovascular disease, myocardial injury, and arrhythmia COVID-19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease Special article-acute myocardial injury in patients hospitalized with COVID-19 infection: a review Heart and lung multimodality imaging in COVID-19 Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19) Cardiac involvement in patients recovered from COVID-2019 identified using magnetic resonance imaging High prevalence of pericardial involvement in college student athletes recovering from COVID-19 Myocardial inflammation and dysfunction in COVID-19-associated myocardial injury 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection Comprehensive health assessment three months after recovery from acute COVID-19 Cardiac troponins for the diagnosis of acute myocardial infarction in chronic kidney disease Use of troponin assay 99th percentile as the decision level for myocardial infarction diagnosis 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation 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 the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging Evaluation of left ventricular global functions with speckle tracking echocardiography in patients recovered from COVID-19 Development of diastolic heart failure in a 6-year follow-up study in patients after acute myocarditis Long-term outcome of patients with virus-negative chronic myocarditis or inflammatory cardiomyopathy after immunosuppressive therapy Myocarditis and inflammatory cardiomyopathy: current evidence and future directions Late detection of left ventricular dysfunction using two-dimensional and three-dimensional speckletracking echocardiography in patients with history of nonsevere acute myocarditis Multimodality imaging approach in the diagnosis of chronic myocarditis with preserved left ventricular ejection fraction (MCpEF): the role of 2D speckle-tracking echocardiography Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging Improved detection of myocardial damage in sarcoidosis using longitudinal strain in patients with preserved left ventricular ejection fraction Myocardial deformation imaging by two-dimensional speckle-tracking echocardiography for prediction of global and segmental functional changes after acute myocardial infarction: a comparison with late gadolinium enhancement cardiac magnetic resonance Evaluation of biventricular function in patients with COVID-19 using speckle tracking echocardiography Subclinical left ventricular dysfunction and correlation with regional strain analysis in myocarditis with normal ejection fraction. A new diagnostic criterion Global longitudinal strain and cardiac events in patients with immune checkpoint inhibitorrelated myocarditis How to cite this article Subclinical myocardial dysfunction in patients recovered from COVID-19