108 Atrial fibrillation effects on coronary perfusion across the different myocardial layers: a computational analysis

Aims Atrial fibrillation (AF) patients may present ischaemic chest pain in the absence of classical obstructive coronary disease. Among the possible causes, the direct haemodynamic effect exerted by the irregular arrhythmia has not been studied in detail. Methods and results A computational fluid dynamics analysis was performed by means of a 1D-0D multiscale model of the entire human cardiovascular system, characterized by a detailed mathematical modelling of the coronary arteries and their downstream distal microcirculatory districts (subepicardial, midwall, and subendocardial layers). Three mean ventricular rates were simulated in both sinus rhythm (SR) and AF: 75, 100, 125 b.p.m. We conducted inter-layer and inter-frequency analysis of the ratio between mean beat-to-beat blood flow in AF compared to SR (Q¯AP/Q¯SR Inter-layer analysis showed that, for each simulated ventricular rate, Q¯AP/Q¯SR progressively decreased from the epicardial to the endocardial layer in the distal left coronary artery districts (P-values < 0.001 for both left anterior descending artery—LAD, and left circumflex artery—LCx), while this was not the case for the distal right coronary artery (RCA) district. Inter-frequency analysis showed that, focusing on each myocardial layer, Q¯AP/Q¯SR progressively worsened as the ventricular rates increased in all investigated microcirculatory districts (LAD, LCx, and RCA) (P-values < 0.001 for all layer-specific comparisons). Conclusions AF exerts direct haemodynamic consequences on the coronary microcirculation, causing a reduction in microvascular coronary flow particularly at higher ventricular rates; the most prominent reduction was seen in the subendocardial layers perfused by left coronary arteries (LAD and LCx).

Electromechanical changes of the myocardium after anthracycline chemotherapy

Funding Acknowledgements Type of funding sources: None. Background and objectives The most common side effects of chemotherapeutics in breast cancer is on the cardiovascular system. Global longitudinal strain (GLS) is the only parameter recommended for follow-up in current guidelines with limited evidence. Other strain imaging parameters and electrical changes after chemotherapy is not well studied. It is not known whether electrical or mechanical changes occur initially. The aim of this study is to evaluate repolarization parameters on ECG and mechanical changes together after chemotherapy in breast cancer patients. Subjects and method Consecutive patients who received chemotherapy due to breast cancer were included. Strain echocardiography and ECGs were performed pre-treatment (T0) and 3rd month after chemotherapy (T2). Additionally, just in three hours of first dose of chemotherapy (T1) another ECG was performed. QT and QT correction for heart rate (QTc), QT dispersion (QT disp) and QTc dispersion (QTc disp), T wave peak to end time (Tpe) and Tpe corrected for QT-QTc measurements were performed (figüre 1 and 2). GLS, longitudinal strain for myocardial layers, circumferential strain (CS), radial strain (RS) and torsion measurements were performed. All mechanical and electrical parameters from different time intervals were compared. Results Thirty-five consecutive patients (35 females, mean age 48.9 ± 11.8 years) who received chemotherapy (mean doxorubicin cumulative dose 415 ± 32 mg/m2) due to breast cancer were included. There was no significant change in mean GLS values before and after treatment (T0 -%18.8 ± 6.82, T1 18.6 ± 3.5 p = 0,863 respectively). However, there was a significant decrease in CS, RS and torsion (T0 -%17,2 ± 3,5, T1-%13 ± 2,84 p <0,001, T0 %45,1 ± 8,3, T1 %35,6 ±10 p <0,001 and T0 %12,1 ± 3.5, T1 %7.7 ± 2.1 p <0,001, respectively). QT, QTc, QTc disp and Tpe, Tpe/QTc parameters were prolonged just after chemotherapy and were still prolonged 3 months after ((QTc: T1 440.01 ± 27.63, T2 468.00 ± 38.98, T3 467.86 ± 35.09), (QTc disp T1 55.48 ± 20.22, T2 78.59 ± 16.15, T3 66.16 ± 14.62), (Tpe (QTc) T1 104 ± 18.52, T2 148.62 ± 19.16, T3 139.77 ± 21.63), (Tpe/QTc T1 0.213 ± 0.05, T2 0.281 ± 0.08, T3 0.258 ± 0.06). Conclusion Electrical and mechanical functions of the heart could be impaired together acutely even three months after doxorubicin chemotherapy. Cardio toxicity should be evaluated in terms of both electrically and mechanically. Abstract Figure. ECG repolarization parameters

Myocardial contractility recovery following acute pressure unloading after transcatheter aortic valve intervention (TAVI) in patients with severe aortic stenosis and different left ventricular geometry: a multilayer longitudinal strain echocardiographicanalysis

Aim of the present study was to describe the left ventricular longitudinal strain (LS) in all myocardial layers in patients with severe aortic stenosis (AS), preserved left ventricular ejection fraction (LVEF) in different LV geometry and to compare LS analysis before and early after acute LV unloading provided by transcatheter aortic valve implantation (TAVI). 68 patients were enrolled. LS was measured from the endocardial layer (Endo-LS), epicardial layer (Epi-LS) and full thickness of myocardium (Transmural-LS) before and after TAVI. Patients were divided in two groups accordingly with relative wall thickness (RWT): concentric LV hypertrophy (cLVH) vs eccentric LV hypertrophy (eLVH). Less impaired values of LS at baseline were observed, in all layers, in patients with cLVHas compared to patients with eLVH (Endo-LS was − 13.2 ± 2 vs − 11.1±3 %, p = 0.041; Epi-LS was − 11.8 ± 1.8 vs − 9.9 ± 3 %, p = 0.043; Transmural-LS was − 12.3 ± 1.8 vs − 10.49 ± 3.3 %, p = 0.02, respectively). A significant improvement in endocardial LS (Endo-LS) after TAVI was detected only in cLVH(− 13 ± 2 vs − 14 ± 2, p = 0.011). Our findings documented that concentric LVH had better basal strain function and showed a better myocardial recovery after TAVI compared to eLVH.

Decreased layer specific longitudinal strain in myocardial segments supplied by stenosed LAD coronary artery: analysis for baseline, peak and recovery phase of stress echocardiography

Background Despite wide utility of global longitudinal strain in the assessment of left ventricular function up to now little is known about layer specific quantification of myocardial function during stress tests and its potential for ischemia detection. Purpose To investigate diagnostic utility of layer specific LS during stress echocardiography using marker segments in patients with established Left Anterior Descending (LAD) coronary artery status. Methods We retrospectively analyzed 63 patients (mean age 62.5±9.9 years, 62% males) with suspected coronary artery disease, who had performed dobutamine stress echocardiography (DSE). Layer specific speckle tracking LS analyses were performed during rest, maximal stress and recovery. As a marker for LAD (segment most probably supplied by this artery) we used mid-anterior left ventricle segments. LAD status were established with coronary angiography or angioCT and consider as significant if ≥70% stenosis was present. Results In our study group 14 patients had significantly stenosed LAD (group 1) and 24 had normal coronaries (group 2). We detected significantly lowered absolute values of strain in endocardial and mid-myocardial layers of segments supplied by stenosed LAD at rest for endocardium −8.6% (group 1) vs −13.4% (group 2); p=0.045; and mid-myocardium −7.3% (group 1) vs −11.2% (group 2); p=0.044. Moreover, we observed similar trend at recovery, however without reaching statistical significance. Conclusions Longitudinal strain analysis focused on segments supplied by assessed coronary artery my provide quantitative data confirming ischemia in the settings of rest and stress echocardiography. Our pilot study suggest that for inotropic agents like dobutamine the potential ischemic dysfunction may be however masked at peak stage of the test. Funding Acknowledgement Type of funding source: None

45 Severe secondary mitral regurgitation due to left ventricular non- compactation cardiomyopathy- a rare cause of heart failure

Introduction Left ventricular non-compaction is a rare form of cardiomyopathy charactherized by the presence of a two layered ventricular wall- a thinner epicardial layer and an inner, non-compacted layer with prominent trabeculations associated with deep, intratrabecular recesses that communicate with left ventricle cavity. Clinical manifestations vary in severity, including symptoms of heart failure, thromboembolic events or arrhythmias. Left ventricular (LV) dysfunction leads to tethering of the mitral apparatus and is a cause for secondary significant mitral regurgitation. Case presentation We report the case of a 57 year-old female patient, diagnosed with severe mitral regurgitation one year before presentation, with severe heart failure (HF) symptoms, referred to our clinic for the surgical replacement of the mitral valve. Clinical examination revealed no signs of pulmonary or systemic congestion and systolic apical murmur. Blood tests were normal, except for the elevated BNP (552 pg/ml). Electrocardiogram showed sinus rhythm and left ventricular hypertrophy. Coronary angiogram did not identify any coronary artery lesions. Echocardiography revealed mildly dilated left ventricle, but wih proeminent trabeculations and two distinct myocardial layers with a non-compacted/compacted ratio of 2:1 in the anterior and lateral walls, diagnostic for left ventricular non-compaction cardiomyopathy. LV ejection fraction was 40% , with severe secondary mitral regurgitation due to significant antero-posterior dilation of the mitral ring, with intact mitral leaflets; mild pulmonary hypertension was present. Magnetic resonance imaging (MRI) identified a two layer antero-lateral myocardium and confirmed the echo diagnosis; there was no evidence of scarring as there was absent late gadolinium enhacement. In the absence of fibrosis on MRI or any arrhythmic events on repeated Holter ECG monitoring, the implantation of a cardiac defibrillator was deferred. Given the secondary cause for mitral regurgitation (LV dysfunction), specific HF medication with beta blocker and renin-angiotensin-aldosterone blockade was initiated and titrated to optimal doses. With medical treatment the evolution was favourable. Currently, 3 years after the initial diagnosis, 6 minutes walk test revealed good functional capacity (510 m), a BNP value of 104 pg/l, without any worsening of LV systolic function nor progression of pulmonary hypertension. Conclusion Left ventricular non-compaction cardiomyopathy is a rare cause of heart failure, but due to advances in imaging modalities and increasing awareness, its prevalence is growing. Its pathogenesis and prognosis largely remain unknown, but early and adequate initiation of neurohormonal medication may be just as essential in order to prevent complications and improve long term prognosis, as for other forms of cardiomiopathy, even in the presence of severe secondary mitral regurgitation.

P4352Usefulness of speckle tracking echocardiography in the detection of ventricular mechanics changes after percutaneous intervention of coronary chronic total occlusions

Background Previous studies show contradictory results of the effect of chronic total occlusions (CTO) revascularization on LVEF. Deformation parameters based on speckle tracking (2D-ST) echo allows the evaluation of the systolic regional function. Purpose To examine the usefulness of 2D-ST to detect changes in regional ventricular mechanics in a consecutive cohort of patients with successful CTO percutaneous revascularization. Methods Prospective study that included 13 consecutive patients (72±8 y, 85% men). Revascularization was justified based on the evidence of viability of the underlying territory. 2D-ST was performed before, one and three months after of the procedure. Based on 16 segments model (n: 208), these were classified in two groups (dependent/non-dependent) according to their relationship with the treated CTO. Strain rate (Sr) and Strain (S) of the three myocardial layers were measured. Results 208 segments analyzed. 62 (30%) perfusion dependent, (mean 5 segments/patient), non-dependent: 146 (70%). During follow-up (median: 3.3 m), there were no significant differences with respect to LVEF (56±6 vs. 59±6, p: 0.2). Although non-dependent segments showed no significant changes of deformation parameters after the procedure, dependent segments showed an increase (Δ) of both the S and Sr, being statistically significant the Δ of the three layers S at 3 months vs. non-dependent. Table 1 PRE POST p Δ Non-Dependent segments (N: 146) S-epicardial −16.6±4.9 −16.0±4.0 0.06 0.6±4.0 S-mesocardiac −17.4±4.8 −16.8±4.2 0.08 0.6±3.9 S-endocardial −18.1±5.1 −17.7±4.9 0.337 0.4±4.5 Sr −1.15±0.4 −1.09±0.4 0.080 0.07±0.47 Dependent segments (N: 62) S-epicardial −13.7±5.8 −16.3±4.5 <0.001 −2.6±5.2* S-mesocardiac −14.7±6.1 −17.0±4.5 <0.05 −2.3±5.2* S-endocardial −15.8±6.7 −17.9±4.9 <0.05 −2.1±5.6* Sr −0.98±0.4 −1.03±0.4 0.353 −0.05±0.42 *p<0.05 ΔNon-dependents vs. ΔDependents. S (%) improvement post RCA CTO treatment Conclusions This study shows that CTO treatment improves regional myocardial function in LV segments dependent on CTO at three months of follow-up, without changes in LVEF. 2D-ST allows to examine the effect of flow restoration, providing new information on the potential short-term benefits of this strategy

P5260Differences in myocardial mechanics between dilated cardiomyopathy and ischemic cardiomyopathy by CMR derived feature tracking strain - A propensity score-matched study

Background Adult heart failure in industrialized nations is primarily due to dilated (DCM) and ischemic cardiomyopathy (ICM). Both diseases are characterized by different pathological pathways. While ICM is predominantly caused by local, subendocardial myocyte necrosis, DCM is characterized by a general myocyte apoptosis involving all myocardial layers. Using feature tracking, longitudinal, circumferential, and radial motion of the left ventricle (LV) can be measured, which allows the function of subendocardial, mostly longitudinal orientated, and subepicardial, mostly circumferential orientated fibers to be assessed independently. Purpose It was the aim of our study to detect differences of LV motion between DCM and ICM patients in a propensity score-matched cohort. Methods Between April 2017 and December 2018 we included 845 patients with a clinical indication for CMR in our tertiary care center registry. Out of this cohort we identified 273 patients with ICM and 126 with DCM. Propensity score matching was used to pair patients in each group based on their indexed enddiastolic volume (EDVi), ejection fraction (EF), septal T1. Feature tracking technique was used for strain analyses quantified on steady state free precession cine CMR images yielding six strain parameters. Results Propensity score matching yielded 59 patients in each group (ICM mean age 59.4±13.0 years, 11 females; DCM mean age 66.5±10.6 years, 15 females; LV-EF 32.6±11.4% vs. 33.0±14.2%, p=0.8178; EDVi 124.2±36 ml/m2 vs. 132.9±42 ml/m2, p=0.0909; native T1 values 1161±66 ms vs. 1164±59 ms, p=0.7049). There was no difference in global longitudinal strain between ICM and DCM patients (−10.9±4.4% vs. −10.6±5.8%, p=0.686), whereas global circumferential strain and radial strain were reduced in DCM patients (−12.0±4.3% vs. −10.31±4.8%, p=0.0190 and 21.1±8.9% vs. 18.0±15.5%, p=0.0386). Conclusion Our data confirm the inherently different mechanics of ICM and DCM patients. While myocardial fibres are globally affected in DCM, myocardial damage is predominantly confined to subendocardial layers in ICM despite equally reduced EF.

P3371Impact of severe aortic stenosis on layer-specific longitudinal strain and its prognostic value

Background Global longitudinal strain (GLS) was used to detect early myocardial dysfunction in patients with aortic stenosis (AS), however few data are currently available on the different susceptibility of specific myocardial layer to increased wall stress and its prognostic role. The present study sought to investigate the relationship between changes in LV multilayer strain and the clinical outcome of patients with severe AS and preserved left ventricle ejection fraction (LVEF). Methods We included in the analysis 211 patients (56% males, mean age 73±12 years old) with severe AS and LVEF≥50%, divided in symptomatic (n=114) and asymptomatic group (n=97), and 50 controls matched for age and sex. Patients with moderate-to-severe concomitant valvulopathy and inadequate acoustic windows for evaluation by speckle tracking analysis were excluded. Clinical, demographic and resting echocardiographic data were recorded, including quantification of 2D GLS, subendocardial LS and subepicardial LS. Results Symptomatic patients had increased LV wall thickness and LV mass index than asymptomatic ones (p<0.001), higher transaortic mean pressure gradients (48±14 vs 44±13 mmHg, p=0.004), and lower aortic valve areas (0.42±0.09 vs 0.45±0.08 cm2/m2, p<0.017). GLS was significantly lower in patients with AS compared to controls, especially in symptomatic group (17.9±3.4 vs 19.1±3.1 vs 20.7±2.1%, p<0.001 in symptomatic, asymptomatic and control groups respectively) suggesting an early, subtle, myocardial dysfunction. In particular, the analysis of layer-specific myocardial deformation revealed a marked difference in both the subendocardial LS (20.1±4.9 vs 21.7±4.2 vs 23.4±2.5%, p<0.001) and subepicardial LS (15.8±3.1 vs 16.8±2.8 vs 18.3±1.8%, p<0.001). At multivariable logistic regression analysis, subendocardial LS was independently associated to symptoms (OR=1.148, p=0.014), together with indexed left atrial volume (OR=1.035, p=0.007) and LV concentric remodelling (OR=2.429, p=0.031). During a mean follow up of 38 months (IQ range 18–60 months), 12 patients with asymptomatic severe AS had a cardiovascular (CV) death. The presence of a subendocardial LS <22% at baseline was associated with a higher rate of CV events at 3 and 5-year follow-up (19% vs 5% at 3-year follow-up, and 22% vs 8% at 5-year follow-up, respectively; log-rank p=0.044). Conclusion In patients with severe AS, LS impairment involves all myocardial layers and is more prominent in the advanced phases of the disease. In this setting, the subendocardial LS appears to be independently associated to symptoms than subepicardial LS. In asymptomatic patients, a reduced value of subendocardial LS is associated with higher CV mortality at 3- and 5-year follow-up.

Impact of aortic stenosis on layer-specific longitudinal strain: relationship with symptoms and outcome

Aims The present study sought to assess the impact of aortic stenosis (AS) on myocardial function as assessed by layer-specific longitudinal strain (LS) and its relationship with symptoms and outcome. Methods and results We compared 211 patients (56% males, mean age 73 ± 12 years) with severe AS and left ventricular ejection fraction (LVEF) ≥50% (114 symptomatic, 97 asymptomatic) with 50 controls matched for age and sex. LS was assessed from endocardium, mid-myocardium, and epicardium by 2D speckle-tracking echocardiography. Despite similar LVEF, multilayer strain values were significantly lower in symptomatic patients, compared to asymptomatic and controls [global LS: 17.9 ± 3.4 vs. 19.1 ± 3.1 vs. 20.7 ± 2.1%; endocardial LS: 20.1 ± 4.9 vs. 21.7 ± 4.2 vs. 23.4 ± 2.5%; epicardial LS: 15.8 ± 3.1 vs. 16.8 ± 2.8 vs. 18.3 ± 1.8%; P < 0.001 for all]. On multivariable logistic regression analysis, endocardial LS was independently associated to symptoms (P = 0.012), together with indexed left atrial volume (P = 0.006) and LV concentric remodelling (P = 0.044). During a mean follow-up of 22 months, 33 patients died of a cardiovascular event. On multivariable Cox-regression analysis, age (P = 0.029), brain natriuretic peptide values (P = 0.003), LV mass index (P = 0.0065), LV end-systolic volume (P = 0.012), and endocardial LS (P = 0.0057) emerged as independently associated with cardiovascular death. The best endocardial LS values associated with outcome was 20.6% (sensitivity 70%, specificity 52%, area under the curve = 0.626, P = 0.022). Endocardial LS (19.1 ± 3.3 vs. 20.7 ± 3.3, P = 0.02) but not epicardial LS (15.2 ± 2.8 vs. 15.9 ± 2.5, P = 0.104) also predicted the outcome in patients who were initially asymptomatic. Conclusion In patients with severe AS, LS impairment involves all myocardial layers and is more prominent in the advanced phases of the disease, when the symptoms occur. In this setting, the endocardial LS is independently associated with symptoms and patient outcome.