Subclinical Myocardial Dysfunction in Patients with Persistent Dyspnea One Year after COVID-19

Long coronavirus disease 2019 (COVID-19) was described in patients recovering from COVID-19, with dyspnea being a frequent symptom. Data regarding the potential mechanisms of long COVID remain scarce. We investigated the presence of subclinical cardiac dysfunction, assessed by transthoracic echocardiography (TTE), in recovered COVID-19 patients with or without dyspnea, after exclusion of previous cardiopulmonary diseases. A total of 310 consecutive COVID-19 patients were prospectively included. Of those, 66 patients (mean age 51.3 ± 11.1 years, almost 60% males) without known cardiopulmonary diseases underwent one-year follow-up consisting of clinical evaluation, spirometry, chest computed tomography, and TTE. From there, 23 (34.8%) patients reported dyspnea. Left ventricle (LV) ejection fraction was not significantly different between patients with or without dyspnea (55.7 ± 4.6 versus (vs.) 57.6 ± 4.5, p = 0.131). Patients with dyspnea presented lower LV global longitudinal strain, global constructive work (GCW), and global work index (GWI) compared to asymptomatic patients (−19.9 ± 2.1 vs. −21.3 ± 2.3 p = 0.039; 2183.7 ± 487.9 vs. 2483.1 ± 422.4, p = 0.024; 1960.0 ± 396.2 vs. 2221.1 ± 407.9, p = 0.030). GCW and GWI were inversely and independently associated with dyspnea (p = 0.035, OR 0.998, 95% CI 0.997–1.000; p = 0.040, OR 0.998, 95% CI 0.997–1.000). Persistent dyspnea one-year after COVID-19 was present in more than a third of the recovered patients. GCW and GWI were the only echocardiographic parameters independently associated with symptoms, suggesting a decrease in myocardial performance and subclinical cardiac dysfunction.

The potential of virtual global mobility: implications for practice and future research

PurposeThe COVID-19 pandemic has forced global organizations to adopt technology-driven virtual solutions involving faster, less costly and more effective ways to work worldwide even after the pandemic. One potential outcome may be through virtual global mobility (VGM), defined as the replacement of personal physical international interactions for work purposes with electronic personal online interactions. The purpose of this article is to establish VGM as a theoretical concept and explore to what extent it can replace or complement physical global work assignments.Design/methodology/approachThis perspectives article first explores advantages and disadvantages of global virtual work and then discusses the implementation of VGM and analyses to what extent and how VGM can replace and complement physical global mobility.FindingsRepresenting a change of trend, long-term corporate expatriates could become necessary core players in VGM activities while the increase of the number of global travelers may be halted or reversed. VGM activities will grow and further develop due to a continued rapid development of communication and coordination technologies. Consequently, VGM is here to stay!Originality/value The authors have witnessed a massive trend of increasing physical global mobility where individuals have crossed international borders to conduct work. The authors are now observing the emergence of a counter-trend: instead of moving people to their work the authors often see organizations moving work to people. This article has explored some of the advantages, disadvantages, facilitators and barriers of such global virtual work. Given the various purposes of global work the authors chart the suitability of VGM to fulfill these organizational objectives.

Pack for Sustainability: Navigating through Uncharted Educational Landscapes

The worlds of education and learning have for the last few decades been characterized by reactions to the detrimental human impact on the environment, which is measured on such a scale that scholars now refer to the present epoch as the Anthropocene. In order to develop ideas and practices that could guide us into place-based research and an emancipatory relationship between pedagogy and knowledge, the focus needs to shift from what to teach and why (Knowledge and Curriculum) and concern over how learning is evaluated (Assessment) to how we should teach (Pedagogy). The acronym PACK (Pedagogy, Assessment, Curriculum, and Knowledge) turned into the idea of packing for a trip into uncharted educational territory, taking with us several gadgets that might be useful. Our own journey emerged as a dialogue between a philosopher and a science educator. Building on experiences from global work to regional research and a university chairmanship for sustainability, we tried to pack some big ideas for educators to take along, helping them navigate the educational landscapes ahead.

164 Effect of cardiac contractility modulation therapy on myocardial work in patients with heart failure with reduced ejection fraction

Aims Cardiac contractility modulation therapy (CCMT) has been shown to reduce hospitalizations and to improve quality of life in heart failure patients with reduced ejection fraction (HFrEF) who remain symptomatic despite disease-modifying therapies. Strain imaging derived myocardial work (MW) is an emerging tool for evaluating left ventricular mechanics by incorporating systolic deformation and afterload burden in the analysis. To evaluate prospectively the impact of CCMT in HFrEF patients on MW derived parameters in relation to standard echocardiographic indices. Methods and results We recruited 12 HFrEF patients with indications to CCMT according to current clinical practice. A comprehensive echo-Doppler evaluation, including speckle tracking derived assessment of global longitudinal strain (GLS), was performed before and after three months from the CCM device implantation. Parameters of MW such as global work index (GWI), global constructive work (GCW) global wasted work (GWW), and global work efficiency (GWE) were calculated according to standardized procedures. Median values (interquartile range) were compared for all those parameters from baseline and 3-month follow-up with Wilcoxon Rank Sum test for continuous variables. At three months from CCM implant an improvement of LVEF [from 32% (27–34) to 36% (29–39), P < 0.05], GLS [from 7.4% (6.2–11.2) to 9.9% (7.5–9.4), P < 0.05], GWI [from 461 mmHg (372–613) to 589 mmHg (413–696), P < 0.05], GCW [from 800 mmHg (620–930) to 970 mmHg (644–1009), P = 0.236], and GWE [from 73% (65–78) to 85% (78–87), P < 0.05] was observed, with a consistent reduction of GWW [from 161 mmHg (148–227) to 125 mmHg (101–188), P < 0.05]. We also found a positive correlation between the magnitude of LVEF improvement and the baseline values of GCW (r = 0.727, P = 0.011). Conclusions At 3 months, CCMT significantly improves standard and advanced left ventricular systolic function indices. This improvement is due to the increase of constructive work and a reduction of wasted work. In addition, the increase of left ventricular ejection fraction can be predicted by the global constructive work levels at baseline.

652 Myocardial work in patients undergoing transcatheter aortic valve implantation: clinical value and implications for outcome

Aims Non-invasive myocardial work (MW) quantification has emerged in the last years as an alternative echocardiographic tool for myocardial function assessment. This new parameter provides a less loading-dependent evaluation of myocardial performance through the combined assessment of global longitudinal strain (GLS) and non-invasive left ventricle (LV) pressures. The role of MW as a marker of cardiac dysfunction and reverse remodelling in patients with severe aortic stenosis (AS) after aortic valve implantation (TAVI) has not been adequately investigated. This study aims to evaluate MW indices as early echocardiographic markers of LV reverse remodelling within a month after TAVI and their prognostic value. Methods and results We conducted a single-centre prospective study, enrolling 70 consecutive patients (mean age 80.1 ± 5.5 years) with severe AS undergoing TAVI between 2018 and 2020, selected from the EffecTAVI registry. Exclusion criteria were prior valve surgery, severe mitral stenosis, permanent atrial fibrillation, left bundle branch block (LBBB) at baseline, and suboptimal quality of speckle-tracking image analysis. Echocardiographic assessment was performed before TAVI and at 30-day follow-up. Clinical, demographic, and resting echocardiographic data were recorded, including quantification of 2D global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). LV peak systolic pressure was estimated non-invasively from the sum of systolic blood pressure and trans-aortic mean gradient. One month after the procedure, there was a significant improvement of LV GLS (−17.94 ± 4.24% vs. −19.35 ± 4.31%, before and after TAVI respectively, P = 0.002), as well as a significant reduction of GWI (2430 ± 586 mmHg% vs. 1908 ± 472 mmHg%, P < 0.001), GCW (2828 ± 626 mmHg% vs. 2206 ± 482 mmHg%, P < 0.001), and GWW (238 ± 207 mmHg% vs. 171 ± 118 mmHg%, P = 0.006). Conversely, MWE did not significantly change early after intervention (90.53 ± 6.05% vs. 91.45 ± 5.05%, P = 0.204). After TAVI, 30 patients (42.8%) developed LV dyssynchrony due to LBBB or pacemaker implantation. When the population was divided according to the presence or absence of LV dyssynchrony at 30-day follow-up, a significant reduction in GWW was found only in those without dyssynchrony (244 ± 241 vs. 141 ± 110 mmHg% with and without dyssynchrony respectively, P = 0.002). Consistently, in this subgroup, MWE significantly improved post-TAVI (90 ± 7 vs. 93 ± 5%, P = 0.002), while a trend of MWE reduction was observed in patients who developed dyssynchrony post-TAVI (91 ± 4 vs. 89 ± 5%, P = 0.164). In the overall population, a baseline value of MWE< 92% was associated with an increased rate of cardiovascular events (composite of all-cause death and rehospitalization for heart failure) at 1-year follow-up (22.2 vs. 3.1%, long rank, P = 0.016). Conclusions In patients with severe AS undergoing TAVI a significant reduction of GWW and improvement of MWE can be detected only in those who did not develop LV dyssynchrony. In this setting, MWE lower than 92% at baseline is associated with poor outcome. Thus, MWE could represent an alternative tool for myocardial function assessment in patients receiving TAVI.

636 Global cardiovascular assessment in patients with PH+ chronic myeloid leukaemia treated with TKI: long-term follow-up

Aims Patients affected by Philadelphia chromosome+ chronic myeloid leukaemia (Ph+CML) undergoing to therapy with tyrosine kinase inhibitors (TKIs) are prone to develop cardiovascular complications, which have relevant prognostic implications. Speckle-tracking echocardiography, allowing strain and myocardial work analyses, can be useful in the early detection of cardiac toxicity. Aim of our study was to assess the cardiotoxic effects of TKIs. Methods We evaluated, at baseline and during FU, 20 patients affected by Ph+ CML (59.7 ± 12.2 years, 13 males), treated Imatinib (52.6%), Nilotinib (36.8%), Ponatinib (5.3%), Dasatinib (5.3%). We measured systolic and diastolic blood pressure (SBP-DBP) and calculated corrected QT interval (QTc). In addition, we analysed echocardiographic parameters including left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), and peak left atrial longitudinal strain (PALS). Cardiovascular (CV) events that we considered were symptomatic or asymptomatic LV dysfunction, acute coronary syndrome (ACS), peripheral artery disease (PAD), and arrhythmias. Results Follow-up (FU) time was 3.4 ± 1 years. Most of patients (63.2%) had cardiovascular risk factors, including arterial hypertension (50%), type2 diabetes mellitus (15%), dyslipidaemia (40%) and cigarette smoking (15%). At the end of FU, SBP was unchanged (128.9 ± 19.6 mmHg vs. 129.1 ± 9.8 mmHg; P=NS) whereas DBP increased (69.4 ± 8.5 mmHg vs. 75 ± 7.7 mmHg; P = 0.004); moreover QTc was longer than baseline (404.4 ± 20.1 ms vs. 424.3 ± 29.8 ms; P < 0.001) and LVEF showed a significant decrease (62.2 ± 3.9% at baseline vs. 59.3 ± 4.8% at FU; P = 0.003); similarly, GCW (2444.1 ± 540mmHg% vs. 2234.7 ± 179.4 mmHg%; P = 0.034), GWI (2158.1 ± 589.6 mmHg% vs. 1923.1 ± 174.5 mmHg%; P = 0.022) and PALS (36.3 ± 17.1% vs. 32.8 ± 9.7%; P = 0.002) decreased during cancer therapy. On the other hand, GLS (−18.6 ± 3.1% vs. −19.4 ± 1.1%; P=NS), GWE (94.3 ± 4.1% vs. 93.6 ± 3.6%; P=NS) and GWW (120.6 ± 94.3 mmHg% vs. 106.3 ± 68.9 mmHg%; P=NS) did not change significantly. CV events were observed in 66.7% of the study population. These were mostly represented by ACS, atrial arrhythmias and symptomatic LV dysfunction (30.7% for each) and, to a lesser extent, PAD (7.6%). By comparing patients with events (group A) with those without events (group B) we found that differently from group B, group A showed during FU a significant increase of DBP (from 66 ± 5.2 mmHg to 71.2 ± 6.1 mmHg, P = 0.010; vs. group B= from 76 ± 12.mmHg to 78 ± 4.1 mmHg, P=NS) and a significant QTc prolongation (from 415.7 ± 16.1 ms to 441 ± 29.8 ms, P < 0.001; vs. group B= from 390.4 ± 19.3 ms to 405.6 ± 23.3 ms, P=NS); as to echocardiographic parameters, we found, in patients with CV events, a significant decrease of: LVEF (from 62.7 ± 4.7% to 58.8 ± 4.3%, P = 0.004; vs. group B from 61.4 ± 2.8% to 60 ± 1.7%, P=NS), GCW (from 2566.2 ± 669.6 mmHg% to 2230.1 ± 199.4 mmHg%, P = 0.021, vs. group B 2194 ± 167.5 mmHg% to 2212.6 ± 160mmHg%, P=NS) and PALS (from 36.1 ± 17% to 29.6 ± 6.6%, P = 0.022 vs. group B from 32.7 ± 8% to 35 ± 8.5%, P = 0.003). Of these parameters, only PALS was significant independent predictor of CV events on logistic regression analysis (OR 0.82 CI 95 0.69–0.98, P = 0.034). Conclusions Advanced echocardiographic parameters, including myocardial work and left atrial strain analysis, are particularly valuable in the early detection of TKI-induced cardiac toxicity. PALS could be an useful tool to predict outcome in these patients.

491 Short-term prognostic implications of left ventricular myocardial work indices in advanced heart failure patients treated with repetitive Levosimendan infusions

Aims Repetitive Levosimendan treatment in advanced heart failure patients has not been investigated yet via myocardial work indices (MWI), which could more accurately detect the effects of this both inotropic and vasodilatory drug. The aims of this study were (1) to describe variations of myocardial work indices, as a consequence of repetitive Levosimendan infusions and (2) to assess the prognostic value of myocardial work parameters in these patients. Methods and results Fourteen patients with advanced heart failure treated with intermittent in-hospital levosimendan infusions were prospectively included. Clinical, laboratory, and echocardiographic assessment were performed before and after every Levosimendan infusion. The primary endpoint was a composite of any episode of decompensated HF, urgent HF rehospitalization, cardiogenic shock, cardiac arrest and cardiovascular death at 4–6 weeks follow-up after each planned infusion. During follow-up (mean: 150 ± 99 days) a total of 37 infusions were performed and a total of 11 cardiovascular events occurred. Global constructive work (GCW), global work efficiency (GWE), and global work index (GWI) increased after Levosimendan infusion in 62.2%, 73.0%, and 70.3% of cases, with significant differences between patients with and without outcomes [delta GCW: −7.36 mmHg% (134.12) vs. 113.81 mmHg% (204.41), P = 0.007; delta GWE: −3.27% (8.38) vs. 4.30% (5.58), P = 0.002]. Delta value of GWE showed the largest area under curve (AUC: 0.82, 95% CI: 0.64–1.00, P = 0.002) for outcome prediction with a cut-off point of 0.5%. Independent prognostic value of GWE variation was confirmed in multivariable regression models (OR: 0.825, 95% CI: 0.702–0.970, P = 0.02). Conclusions GWE and GCW provided incremental and independent prognostic value at short-term follow-up over traditional echocardiographic parameters. The differentiation of patients into ‘workers’, whose GWE improved after Levosimendan infusion, and ‘non-workers’, who failed to improve their GWE, permitted to identify patients at higher risk of forthcoming cardiovascular events. Monitoring these patients with MWI may have relevant clinical implications.

710 Advanced echocardiographic analysis to identify cardiac toxicity after TKI exposure in patients with CML

Aims Worsening of cardiac function with increased arrhythmic risk is common in cancer patients undergoing chemotherapy. Impaired LV global longitudinal strain (GLS) in these patients despite preserved ejection fraction is a common issue. Recently, myocardial work by speckle-tracking echocardiography has been used to overcome GLS limitations in various conditions, but little is known about its usefulness in the detection of cardiac toxicity. Moreover, left atrial (LA) toxicity may occur early in the course of cancer therapy. The main aim of the study was to assess the cardiotoxic effects of tyrosine kinase inhibitors (TKIs) on patients with Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) by using novel echocardiographic tools as myocardial work and atrial strain analysis. Methods and results We retrospectively enrolled Ph+ CML patients treated with TKIs followed at the cardio-oncology outpatient clinic of our hospital from December 2018 to March 2019 who underwent clinical evaluation with ECG and echocardiogram (TTE) before and after 1 year of treatment with TKIs. Healthy subjects were enrolled in the control group matched for gender, age and cardiovascular risk factors. Myocardial work was derived from the strain-pressure relation, integrating in its calculation the non-invasive arterial pressure. LA longitudinal strain (reservoir, conduit, and booster) was obtained from an optimized apical 4-chamber view of the LA. The study recruited 32 patients in Ph+ CML group and 32 healthy controls. 39% of patients were treated with Imatinib, 29.3% with Nilotinib, 4.9% with Dasatinib and 4.9% with Ponatinib. Main results are detailed in Table 1. At 1-year follow-up there was a significant reduction compared to baseline in global constructive work (2555.22 ± 564.33 vs. 2119.31 ± 700.19; P = 0.0001), global work efficiency (96.13 ± 1.90 vs. 94.00 ± 2.96; P = 0.002), and global work index (2340.75 ± 579.57 vs. 1938.46 ± 680.23; P = 0.001), and a non-significant reduction in global wasted work (P = 0.393). Regarding left atrial strain analysis at the 1-year follow-up there was a statistically significant reduction in LA contractile strain (booster= 14.63 ± 1.408 vs. 12.38 ± 1.581; P = 0.018). LA contractile strain reduction was also observed in the comparison with controls (12.38 ± 2.99 vs. 14.91 ± 3.09; P = 0.009). Any other significant difference was detected between baseline and FU TTE data in the Ph+ CML group. Conclusions New imaging methods for the study of cardiotoxicity provide an additional tool for early prediction of potential adverse effects of antineoplastic drugs. TKIs therapy leads to an impairment of atrial contractility, which can be detected by atrial strain e myocardial work analysis.

709 Non-invasive assessment of myocardial work: an useful tool for predicting LV remodelling after myocardial infarction?

Aims Left ventricular function recovery (LV-REC) or left ventricular adverse remodelling (LV-REM) after acute myocardial infarction (AMI) play an important role for identifying patients at risk of heart failure. In this study we aim to evaluate the usefulness of non-invasive myocardial work (MW), a new index of global and regional myocardial performance, to predict LV-REC or LV-REM after AMI. Methods and results Fifty patients with AMI (mean age, 63.8 ± 13.4 years), treated by primary percutaneous coronary intervention (PCI), were prospectively enrolled. They underwent a baseline transthoracic Doppler echocardiography (TTE) within 48 h after PCI and a second TTE after a median of 31 days during the follow-up. MW was derived from the strain-pressure loops, integrating in its calculation the non-invasive arterial pressure, according to standard speckle tracking echocardiography recommendations. LV-REC was defined as an absolute improvement of left ventricular ejection fraction (LVEF) ≥ 5% from LVEF at baseline, whereas LV-REM was defined as an increase of ≥ 20% of the LV end diastolic volume (LVEDV) at 1 month follow-up. We overall found a significant improvement from baseline to one-month follow-up for values of LVEF (49.8 ± 9.5% vs. 52.8 ± 9.3%, P = 0.001), global longitudinal strain (GLS) (−13.4 ± 3.9% vs. −18.7 ± 5.4%, P = 0.016), global work index (GWI) (1368.6 ± 435.2 vs. 1788 ± 493 mmHg/%, P = 0.0001), global work efficiency (GWE) (89.96 ± 9.3% vs. 91.3 ± 6.4%, P = 0.001), global constructive work (GCW) (1619.16 ± 497.9 mmHg/% vs. 2008.6 ± 535.3 mmHg/%, P = 0.0001), global wasted work (GWW) (188.8 ± 19.8 mmHg/% vs. 149.2 ± 16.5 mmHg/%). However, LV-REC at 1 month of follow-up was observed only in 36% of the population enrolled, whereas LV-REM was described in 18% of cases. Using ROC curve analysis, we identified a cut off value of 202 mmHg/% for baseline GWW (sensitivity 75%, specificity 62%, AUC 0.6667, CI 95%: 0.51618–0.81715, P = 0.0001) to identify patients with LV-REM at 1 month. With regards to conventional echo parameters, patients with LV-REC showed lower baseline wall motion score index (WMSI) than those without LV-REC (1.73 vs. 1.38, P = 0.007). Conclusions Among standard and advanced TTE parameters, only baseline GWW is able to predict early LV-REM at 1 month after primary PCI. Therefore, it could be used during baseline evaluation of AMI patients for a more accurate stratification of those at higher risk of heart failure. However, further larger scale studies are needed to validate these findings.

227 Myocardial work evaluation in severe aortic stenosis undergoing transcatheter aortic valve implantation

Aims Myocardial work (MW) is a novel echocardiographic technique which assesses left ventricular (LV) performance through LV pressure-strain loops. MW corrects speckle tracking echocardiography (STE)-derived parameters for afterload using non-invasive systolic blood pressure (SBP) as a surrogate for LV systolic pressure. In patients with severe aortic stenosis (AS), the corrected MW (cMW) has been proposed, consisting in adding the mean aortic gradient in SBP. This method revealed to be feasible and reliable, demonstrating good correlation with invasively measured LV systolic pressure. To evaluate myocardial performance of patients with severe AS, before and after transcatheter aortic valve implantation (TAVI), by MW indices. Methods patients with severe AS undergoing TAVI were included. Transthoracic, standard echocardiography and STE were performed the day before the procedure and within 2 days after. MW was calculated by combining STE-derived indices with non-invasively estimated LV systolic pressure. Results 30 patients (79±5 years old, 56% females) with severe AS (mean gradient 47±14 mmHg, aortic valve area 0.6±0.1 cm2), and eligible for TAVI were enrolled. Baseline global longitudinal strain was impaired (GLS −15±4%), in presence of normal LV ejection fraction (LVEF 57±10%). Corrected global work index and global constructive work were preserved at baseline and markedly decreased after TAVI (cGWI 2322±791 vs. 1710±505 mmHg%, P=0.001; cGCW 2774±803 vs. 2083±536 mmHg%, P=0.0007). Corrected global wasted work and global work efficiency were respectively higher and lower than reference values existing in literature, and no significant changes were observed after TAVI (cGWW 276±174 vs. 277±165 mmHg%, P=0.974; cGWE 89±5 vs. 87±5%, P=0.177). A significant inverse correlation was found between baseline cGWI and left atrial volume index (r = −0.5, P=0.03). Conclusions Patients with severe aortic stenosis and preserved LVEF show a good LV performance before and after TAVI, with a significant decrease in MW indices after TAVI, because of the reduced afterload due to AS treatment. The negative correlation between left atrial volume and cGWI may reflect the extent of myocardial damage in AS. However, further studies with larger sample size and appropriate follow-up are needed to evaluate the role of MW in prognosis and risk stratification of this subset of patients.