Djordievic-Dikic, Ana

Abstract Background Cardiovascular abnormalities have been observed in half of all COVID-19 patients in the acute phase of the infection. Additionally, 10-35% of these patients have various long-term symptoms diagnosed with post-acute sequelae of COVID-19 (PASC). Aim of this study was to evaluate the role of exercise stress echocardiography (ESE) with an integrated approach, inclusive of Speckle-Tracking Echocardiography (STE) with Myocardial Work (MW) analysis in the evaluation of patients after COVID infection. Methods We prospectively recruited a population of 370 post-COVID 19 patients (Group 1) (225 males; 55.8 ±8.3 years), and of 250 age- and sex-comparable healthy controls (Group 2). In Standard Doppler echocardiography, STE and MW analyses and lung ultrasound at rest and at peak supine-bicycle ESE were performed. Results Left ventricular (LV) wall thickness, diameters and mass index were comparable between the two groups. Both LV ejection fraction (EF) and right ventricular (RV) functional indexes (TAPSE and Tissue Doppler S’ wave) at rest did not show differences between the two groups. Conversely, baseline LV GLS (-16.2±2.8 vs. –20.4±3.3 %; p<0.01), MW efficiency (88.8±3.2 vs. 93.2±3.3 %; p<0.001), and RV strain (-16.4±2.8 vs. –20.4±4.3 %; p<0.01), were significantly reduced in Group 1. Also pulmonary artery systolic pressures (PASP) (33.5±3.8 vs. 24.6±3.1 mmHg; p<0.001), and LV E/e’ ratio were significantly increased in COVID group, while B-lines ( ≥ 2) at rest were found in 25.3% of Group 1 and 5.1% of Group 2 (p < 0.001). During effort, COVID patients showed reduced exercise time and exercise capacity (<0.001). Values of LVEF, RV strain and LV GLS (all with p value <0.01) and MWE (p<0001) were much lower in COVID patients when compared to Group 2. Additionally, COVID patients showed at peak effort an increased LV E/e’ ratio, pulmonary pressures and B-lines by lung ultrasound (all p <0.001). Multivariable analysis detected independent associations of baseline GLS and MWE with maximal workload (watts reached), LV E/e’ ratio and B-lines during effort (p<0.001), stronger than the association of LVEF with the same functional parameters (p<0.01). What’s more, RV strain (p<0.001) was significantly associated with PASP levels at peak effort. Conclusions In post-COVID patients, biventricular involvement with impairment of LV and RV systolic function is frequent, missed by conventional indices such as EF or TAPSE, and detected by more sensitive STE indices such as LV-GLS, ME, and RV-strain. These alterations are functionally significant and associated with shorter exercise -time, more pulmonary hypertension, and greater pulmonary congestion during stress.

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021–2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

Stress echo (SE) 2030 study is an international, prospective, multicenter cohort study that will include >10,000 patients from ≥20 centers from ≥10 countries. It represents the logical and chronological continuation of the SE 2020 study, which developed, validated, and disseminated the “ABCDE protocol” of SE, more suitable than conventional SE to describe the complex vulnerabilities of the contemporary patient within and beyond coronary artery disease. SE2030 was started with a recruitment plan from 2021 to 2025 (and follow-up to 2030) with 12 subprojects (ranging from coronary artery disease to valvular and post-COVID-19 patients). With these features, the study poses particular challenges on quality control assurance, methodological harmonization, and data management. One of the significant upgrades of SE2030 compared to SE2020 was developing and implementing a Research Electronic Data Capture (REDCap)-based infrastructure for interactive and entirely web-based data management to integrate and optimize reproducible clinical research data. The purposes of our paper were: first, to describe the methodology used for quality control of imaging data, and second, to present the informatic infrastructure developed on RedCap platform for data entry, storage, and management in a large-scale multicenter study.