Myocardial work and left atrial function, by speckle tracking echocardiography, are the only independent predictors of mid-term mortality in HFpEF

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by 2 National grants of Romanian Ministry of Research and Innovation - UEFISCDI (PN-III-P1-1-TE-2016-0669, acronym Heart-Preserved and PN-III-P1-1.2-PCCDI2017-0527, acronym BIOVEA). OnBehalf HEART-PRESERVED Background. Heart failure with preserved ejection fraction (HFpEF), defined by the 2021 ESC guidelines and the new universal definition, is one of the most challenging diagnosis in cardiology. Parameters for predicting mortality in HFpEF are still debatable. Left atrial (LA) function and myocardial work (MW) by speckle-tracking echocardiography (STE) might be promising tools for predicting mortality in HFpEF. Methods. We assessed 88 patients (67 ± 9 years, 33 men) with HFpEF (mean NTproBNP of 357 ± 350 pg/ml) by 2D echo, STE, and CMR. By echo we measured LV ejection fraction (LVEF), E/E’, sPAP, left atrial volume indexed (LAVi), and global longitudinal strain (GLS). We assessed LA function by 2DSTE: reservoir function by strain from MVC to MVO (LASr) and positive strain rate (LASRr), conduit function by strain from MVO to onset of atrial contraction (LAScd) and early negative strain rate during conduit phase (LASRcd), and LA pump function by negative strain at MVC (LASct) and late negative strain rate during atrial contraction phase (LASRct) (Figure 1); and MW by 2DSTE: global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), as GCW/(GCW + GWW) in %. By CMR we evaluated LVEFcmr, LV mass, T1 mapping with mean extracellular volume (ECVm), and pre-gadolinium times quantification (preGDT1m) as markers of myocardial fibrosis. A follow-up visit for cardiovascular mortality was performed by phone at 18 months from the baseline visit. Results. 12 patients died during follow-up (14%). Comparing non-survivors vs. survivors (see tables from Figure 2), NTproBNP level and LV mass were significantly higher in non-survivors (P &amp;lt; 0.001); meanwhile, GWE was lower, whereas GWW was higher in non-survivors vs. survivors. Moreover, LASRct was lower in non-survivors vs. survivors. All the other echo or CMR parameters, including markers of myocardial fibrosis were not different between non-survivors and survivors (Figure 2). By multiple regression analysis, GWE &amp;lt; 92% (AUC = 0.72, p = 0.018) and LASRct &amp;lt;-1 (AUC = 0.70, p = 0.014) were the only independent predictors of mortality, from all conventional echo, STE, and CMR parameters. Conclusions LV assessment by myocardial work and LA assessment by STE are the only independent predictors of mid-term mortality in HFpEF. Abstract Figure. LA deformation analysis  Abstract Figure. Survivors vs non-survivors </jats:sec

Multimodality imaging approach by speckle tracking echocardiography and cardiac magnetic resonance of heart failure with preserved ejection fraction, a step forward

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Project No. PN-III-P1-1-TE-2016-0669, within PNCDI III, and grant 5/2018 and 83/2018 Background. Heart failure with preserved ejection fraction (HFpEF), defined by 2016 guidelines and new 2019 scoring system, is one of the most challenging diagnosis in cardiology. A better understanding of this entity might provide us a better way to treat. Myocardial work (MW) by speckle-tracking echocardiography (STE) might be a promising tool for analysis of myocardial function. However, there is no data on MW changes in HFpEF patients. Methods. We assessed 94 patients (67 ± 9 yrs, 33 men) with HFpEF (NTproBNP of 349 ± 418 pg/ml), by 2D and STE, and compared them with 25 normal, age-matched, subjects; 80 patients had also a CMR evaluation. We measured LV ejection fraction (LVEF), mean E’ (E’m), E/E’, sPAP, left atrial volume indexed (LAVi), and global longitudinal stain (GLS). We assessed MW by 2DSTE: global constructive work (GCW), as the "positive" work of the heart; global wasted work (GWW), as the "negative work"; global work efficiency (GWE), as GCW/(GCW + GWW) in %. We evaluated by CMR LVEFcmr, LV mass, T1 mapping with mean extracellular volume (ECVm), and pre-gadolinium times quantification (preGDT1m) as markers of myocardial fibrosis. Results. Feasibility of the MW analysis was 97%. As expected, E/E’ and sPAP were higher, while GLS was lower in HFpEF patients. GCW did not change, whereas GWW increased and GWE decreased significantly in HFpEF patients (Table). NTproBNP correlated with sPAP, LAVi, preGDT1m, and ECVm. ECVm was the only independent predictor of NTproBNP level (r = 0.40, p = 0.04). GWE corelated significantly with E’m, LVEFcmr, LV mass, and preGDT1m (all r &amp;gt; 0.40, p = 0.001). GWW corelated significantly with sPAP, E/E’ ratio and E’m, LVEFcmr and LVmass, preGDT1m, and ECVm  (all r &amp;gt; 0.4, p &amp;lt; 0.05). GWW was best predicted by a model composed by E"m, LVmass, preGDT1m (r = 0.5, r2 = 0.25, p = 0.003).  Conclusion. MWE decreases, whereas WW increases in HFpEF. Both parameters corelates significantly with diastolic dysfunction parameters, LV mass, LVEF, and most important with myocardial fibrosis markers evaluated by CMR. ECVm by CMR was the only independent predictor of NTproBNP. Therefore, new parameters of myocardial work, derived from 2DSTE, might provide a better understanding of HFpEF. Table.Comparison between groups Group LVEF (%) E/E’ sPAP (mmHg) GLS (%) GWE (%) GCW (mmHg%) GWW (mmHg%) Controls (25) 58 ± 6 7.3 ± 2.4 23.2 ± 8.1 -21.5 ± 2 95.5 ± 1.8 2282 ± 552 87.9 ± 39.6 HFpEF (91) 60 ± 5.7 11.3 ± 3.5 34.3 ± 8.3 -18.2 ± 3 93.7 ± 3.9 2295 ± 279 119.6 ± 79.8 P value 0.09 &amp;lt;0.001 &amp;lt;0.001 0.01 0.03 0.90 0.03 Abstract Figure. Myocardial work assessment </jats:sec

Left atrial volumes evaluation by cardiac magnetic resonance - time to revise the grading severity cut off values

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant of Ministery of Research and Innovation, CNCS-UEFISCDI, project number grant 5/2018 and 83/2018 and PN-III-P1-1-TE-2016-0669, within PNCDI III Background Left atrial maximal volume (LAVmax) assessed by 2D echocardiography (2DE) is incorporated in new scoring system (2019) of heart failure with preserved ejection fraction (HFpEF), using well established cut-off values for grading severity. These values have strong evidence for diagnosis and prognosis. Moreover, cardiac magnetic resonance (CMR) is also included in the structural evaluation of HFpEF. However, cut-off values for LAVmax evaluated by CMR are higher. This might generate a different classification for LA dilation by CMR, potentially including patients in another risk class. We aimed to evaluate LAVi by 2DE and CMR in a group of HFpEF patients, in order to test the agreement between these two methods, regarding severity grading. Methods.  We prospectively enrolled 74 HFpEF patients (68 ± 9 yrs), and evaluate them by 2DE and CMR. Conventional 2DE was used to define anatomy and function of the left ventricle (LV). NTproBNP was done in all patients. We assessed biplane LAVmax index (LAVimax) and LA minimal volume index (LAVimin), from 4C and 2C views, and reported as a mean value, by eco and CMR (area–length method). Cohen"s k of agreement was evaluated to determine if there was an agreement between eco and CMR, using the cut off values for LAVimax by CMR and eco, provided by the guidelines (Figure) Results. Feasibility of the complete analysis was 95% (70 pts). LVEF was 60 ± 5.7%. LAVimax and LAVimin by eco and CMR were highly correlated (all R &amp;gt; 0.7, p &amp;lt; 0.001) (Table). However, CMR diagnosed a high percent of patients as having normal LAVimax values, by comparison with echo (59 vs. 5.7 %, p &amp;lt; 0.001) (Figure). There was no agreement between these two evaluation methods (Cohen"s k of agreement = 0.000), suggesting that CMR evaluation provides completely  different severity grading. NTproBNP significantly correlated only with LAVimin by CMR (R = 0.4, p = 0.04). Conclusions. We suggest that there is need for a future update of the grading cut-offs for LAV by CMR with larger reference range studies, and also with prognosis studies, as 2DE already provided. The present CMR grading severity might generate misclassification in certain pathological condition, such as HFpEF. We also suggest that LAVi min, instead of LAVi max should be used in the future study for assessment of prognosis. LA volumes evaluation by CMR and 2D echo LAVimax LAVimin ECO (ml/m2) 47 ± 11 23 ± 9 CMR (ml/m2) 51 ± 15 26 ± 12 R coefficient 0.7 0.74 P value &amp;lt;0.001 &amp;lt;0.001 Abstract Figure. </jats:sec

Multimodality approach by cardiac magnetic resonance and biological markers in left ventricular non-compaction with heart failure with preserved ejection fraction - revealing the unknown

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): PN-III-P1-1-TE-2016-0669, within PNCDI III Background Left ventricular non-compaction (LVNC) is associated with an increased risk of heart failure (HF). The presence of a real LVNC with HF with preserved ejection fraction (HFpEF), is still controverted. Methods We evaluated prospectively 42 patients with HFpEF, 21 with LVNC (61 ± 9 years) and 21 without LVNC (LVC), aged and risk factor matched, by cardiac magnetic resonance (CMR) 1.5T. LVNC diagnosis was confirmed by Petersen and Jacquier criteria (NC/C ratio and the percentage of NC myocardium). We performed myocardial T1 mapping (normal value of 950 ± 21ms). We calculated a mean value of all native T1 (T1mean), and also for apical (apicalT1) and basal segments (basalT1). We also calculated ECV mean, basal and apical. All patients had NTproBNP and biomarkers for systemic inflammation (hsCRP, IL6, cystatin C and sST2), endothelial dysfunction: VCAM, von Willebrand factor (vWf), vWF metalloproteinase-ADAMTS13, and myocardial fibrosis: vascular peroxidase (VPO), and Galectin-3. Results In the LVNC, mean NC/C ratio was 2.9 ± 0.5 mm and the percentage of NC myocardium was 24.41 ± 8.8%. LVNC patients had significantly higher T1apical, higher ECVmean, ECV basal and apical (Table) by comparison with LVC group, suggesting an extensive fibrosis in LVNC group with significantly higher apical fibrosis.  Inflammatory markers were similar between groups, LVNC patients had lower values of ADAMTS13, suggesting endothelial dysfunction, and higher values of Galectin-3, suggesting increased myocardial fibrosis (Table). Galectin-3 correlated positively only with apicalT1 (R = 0.49, p = 0.04). NTproBNP significantly correlated with VPO, a promotor of fibrosis (r = 0.61, p = 0.009) in LVNC group, whereas in LVC group correlated with cystatin C (r = 0.62, p = 0003) and VCAM (r = 0.4, p = 0.05). Native apical T1 cut off &amp;gt;1021 ms provided the highest sensibility and specificity to differentiate segments with and without NC in HFpEF (p = 0.002) (Figure). Conclusion  HFpEF patients with LVNC have significant higher NTproBNP, higher fibrosis than patients without LVNC, more extensive in non-compacted apical segments. Galectin-3 level correlates only with apical fibrosis on CMR, expressed by apicalT1 time. Moreover, endothelial dysfunction seems to play an important role in HFpEF generation in LVNC. All findings suggests that LVNC is a stand alone condition, not an adaptive hyper-trabeculation in HFpEF. Table.Comparison between groups NTproBNP (pg/ml) Galectin3 (ng/ml) ADAMTS13 (ng/ml) T1mean (ms) basalT1 (ms) apicalT1 (ms) ECV mean (%) ECV basal (%) ECV apical (%) LVNC 294 ± 282 8.44 ± 3.45 767.35 ± 335.56 1013.8 ± 31.8 1002.8 ± 27.2 1059 ± 73 27.2 ± 2.9 26.2 ± 2.9 29.6 ± 3.9 LVC 163 ± 71 6.67 ± 2.88 962.33 ± 253.78 1003.2 ± 28.1 1004.3 ± 29.5 1007 ± 40 24.3 ± 2.5 24.2 ± 2.7 25.2 ± 2.8 P value 0.031 0.048 0.049 0.26 0.865 0.007 0.002 0.033 &amp;lt;0.001 Abstract Figure </jats:sec

Systemic inflammation in the acute myocardial infarction can predict early negative left ventricular remodeling assessed by myocardial work analysis

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): UEFISCDI Background. Left ventricular (LV) remodeling after acute myocardial infarction (AMI) is an important predictor of heart failure (HF). Systemic inflammatory response in the acute phase of AMI is of particular interest, while the relation to the remodeling process is still under debate. New imaging techniques derived from speckle tracking echocardiography (STE), such as myocardial work (MW), are attractive tools since they can detect myocardial remodeling before decrease of global LVEF. However, there is insufficient data regarding MW in AMI patients, and its relation to the inflammatory process. Methods. We assessed 57 patients (53 ± 9 years, 45 men, 64% smokers, 59% hypertensive, 54% with type 2 diabetes) with AMI, by clinical, 2D echo, and STE. Biomarkers panel was evaluated within the first 24 hours from admission: hsTpI and CRP. A second visit with clinical and echo assessment was performed at 6-8 weeks from the baseline visit. Exclusion criteria were unstable patients, non-sinus rhythm, significant valvular disease (&amp;gt;grade 2), other significant pathologies leading to decreased life expectancy, and low quality 2DE. At both visits, global longitudinal stain (GLS) and MW by 2DSTE were measured, on top of conventional echo parameters: global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE) (Figure 1: upper panel - an example of a patient with increase of GWE from baseline to visit 2 ; lower panel - an example of a patient with decrease of the GWE from baseline to visit 2). Results. At baseline, myocardial necrosis by hsTpI significantly corelated with GLS (r = 0.44, p = 0.001) and MW (GWI: r=-0.44, p = 0.001; GCW: r=-0.40, p = 0.002), but not with LVEF. However, systemic inflammation by CRP did not correlate with LVEF or any of the STE parameters.  Interestingly, systemic inflammation by CRP significantly correlated with changes of MW between the two visits: for GWE r=-0.53, p &amp;lt; 0.001; and for GWW r = 0.48, p &amp;lt; 0.001 (Figure 2). A CRP level &amp;gt;28 mg/l was able to predict decrease of GWE from baseline to visit 2. Conclusions. Magnitude of necrosis, expressed by hsTpI, corelates only with GLS and MW parameters, but not with LVEF. CRP level in the acute phase of AMI correlates with myocardial work changes, as an early marker of negative LV remodeling. Abstract Figure 1  Abstract Figure 2 </jats:sec

Time to solve the puzzle of heart failure with preserved ejection fraction by biomarkers, echocardiography and cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): HEART PRESERVED onbehalf HEART PRESERVED Background Heart failure with preserved ejection fraction (HFpEF) is now recognized as a major and growing public health problem worldwide. Clinical trials investigating different treatment strategies had disappointing results. Several biomarkers of inflammation, endothelial dysfunction, and myocardial fibrosis appeared to be promising in understanding HFpEF pathophysiology. Methods. We enrolled prospectively 94 patients with HFpEF in sinus rhythm  (according to 2019 scoring system) (67 ± 9 yrs, 33 men). We evaluated them by 2D and speckle tracking echocardiography (STE). 80 patients had also a cardiac magnetic resonance (CMR) 1.5T evaluation. We measured LV ejection fraction (LVEF), mean E’ (E’m), E/E’ ratio, sPAP, left atrial volume indexed (LAVi), and global longitudinal stain by STE (GLS).  By CMR we evaluated LVEFcmr, LV mass, T1 mapping with mean extracellular volume (ECVm), and pre-gadolinium mean times quantification (preGDT1m) as markers of myocardial fibrosis. All patients had NTproBNP and biomarkers for systemic inflammation (IL6, cystatin C, pentraxin-3, GDF15), endothelial dysfunction: soluble E -selectin, VCAM, von Willebrand factor (vWf), and myocardial fibrosis: Galectin-3. Results. LVEF was 60.5 ± 6 % and LVEFcmr 61 ± 6.6%. All parameters from the scoring system were as we expected: E’m = 7.6 ± 1.8 cm/s, E/E’ ratio = 11 ± 3.4, sPAP = 34 ± 8 mmHg, LAVi = 47 ± 11 ml/m2, GLS=-18.3 ± 2.9, and NTproBNP of 282 ± 294 pg/ml. NTproBNP significantly correlated with sPAP, LAVi, preGDT1m, ECVm, galectin-3, GDF15, and pentraxin-3 (all r &amp;gt; 0.4, p &amp;lt; 0.05). The best predictor for NTproBNP level was GDF15 (r = 0.4, r2 = 0.25, p = 0.001). LAVi significantly corelated with E/E’ ratio, sPAP, NTproBNP, galectin-3 (r &amp;gt; 0.4, p &amp;lt; 0.05). GLS correlated with LVEFcmr, LV mass, ECVm, preGDT1m, LAVi, E/E’ ratio, NTproBNP, GDF15, vWf, Eselectin, VCAM (all r = 0.4, p &amp;lt; 0.05). The best predictor model for GLS was LV mass, NTproBNP, E-selectine, and vWf (r = 0.67, r2 = 0.45, P &amp;lt; 0.001). sPAP was best predicted by a model composed by IL6, VCAM, LAVi (r = 0.5, r2 = 0.25, p &amp;lt; 0.001). E’m significantly correlated with vWf, GHD15, VCAM, LV mass, and preGDT1 (all r &amp;gt; 0.4, p &amp;lt; 0.05), but the best predictor model included only LV mass and GDF15 (r = 0.57, r2 = 0.32, P &amp;lt; 0.001). Galectin-3 significantly correlated with LAVi, preGDT1m, and NTproBNP, but the only predictor for galectin-3 level was preGDT1 (r = 0.4, r2 = 0.2, p = 0.007). Conclusions In HFpEF NTproBNP is significantly correlated with markers of inflammatory status, endothelial dysfunction, and fibrosis, but the level is mainly determined by inflammation (GDF15). Diastolic dysfunction parameters are mainly correlated with inflammatory and endothelial dysfunction biomarkers . Only LAVi was correlated with myocardial fibrosis. Sub-clinical systolic dysfunction is mainly determined by proinflamatory status and endothelial dysfunction, but not by fibrosis. </jats:sec

Left atrial function by speckle tracking echocardography in HFpEF v1

AIMS. None of the conventional echocardiographic parameters alone predict increased NTproBNP level and symptoms, making diagnosis of heart failure with preserved ejection fraction (HFpEF) very difficult in some cases, in resting condition. We will evaluate LA functions by 2D speckle tracking echocardiography (STE) on top of conventional parameters in HFpEF and preHF patients with diastolic dysfunction (DD), in order to establish the added value of the LA deformation parameters in the diagnosis of HFpEF. METHODS. We will enroll patients with HFpEF and compare them with asymptomatic patients with similar risk factors with DD (preHF). We will evaluate them by NTproBNP, conventional DD parameters, and STE. Global longitudinal strain (GS) was added. LA reservoir (R), conduit (C), and pump function (CT) were assessed both by volumetric and STE. 2 reservoir strain (S) derived indices were also measured, stiffness (SI) and distensibility index (DI). </p