605 Assessment of intracardiac flow dynamics for the evaluation of patients with cardiac resynchronization therapy

Aims Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure (HF), reduced left ventricular ejection fraction (EF ≤ 35%) and high-grade intraventricular conduction delays. CRT improves cardiac function, symptoms and well-being, and reduces morbidity and mortality in this setting. However, there are patients unresponsive to CRT. Responders show reverse ventricular remodelling, volumes and diameters reduction, and EF improvement. Noninvasive cardiovascular imaging for visualization and quantitation of intracardiac flows and turbulences has not been assessed thoroughly in CRT. This study seeks to evaluate if the quantitative analysis of intracardiac flow dynamics in HF patients treated by CRT might provide additional information for device optimization and clinical response. Methods and results Fifteen HF patients (five females, age 69.6 ± 9.4 years, NYHA class II/III, EF 29.3 ± 4.6%) were enrolled in the study. Eleven had primitive dilated cardiomyopathy and four had post-ischaemic etiology with completed revascularization. Pacemaker-dependent cases were excluded. MyLab™ X8 platform was used for echocardiographic assessment of intracardiac flow dynamics performed on apical three chamber views. All examinations were realized in baseline (active CRT) and after 5 min of biventricular pacing switch off. The hyperDoppler software was used to assess intracardiac vortexes properties. The analyzed parameters were: vortex area, vortex length, vortex depth, and kinetic of energy dissipation (ΔKE). Categorical variables are expressed as numbers and percentages. Quantitative variables are expressed as mean and standard deviation (SD). Shapiro–Wilk test, D’Agostino Pearson test, and visual inspection of Q–Q-plots were executed to evaluate if variables were normally distributed. Quantitative variables were evaluated with paired sample T-test or Wilcoxon test when appropriate. Clinical features, biochemical parameters, electrocardiograms with and without cardiac pacing, and EF before and after CRT implantation were collected. Although no difference was observed in vortex area/depth/length, a significant increase in KE dissipation after switching OFF the CRT devices (from 1.2 ± 0.9 to 3.5 ± 2.3 J, P < 0.03) was remarkably observed. According to EF improvement after CRT, the patients were divided in responders (5% increase in EF, N = 10) and non-responders (N = 5). Moreover, by analysing the extent of QRS dispersion and the variation of KE dissipation in spontaneous rhythm and after silencing the biventricular pacing, a positive ventricular remodelling (QRS 141.3 ± 29.3 vs. 154.4 ± 24.4ms, P = 0.02; KE dissipation 0.92 ± 0.87 J in responders and 1.53 ± 1.76 J in non-responders, P = 0.006) was detected in responders. Conclusions Noninvasive intracardiac flow dynamics in HF patients represents a complementary tool to standard echocardiography, and provides additional parameters for assessing prognosis and outcomes in CRT recipients. The impact of maladaptation in intracardiac flow dynamic on progressive LV remodelling could be useful to evaluate the prognostic meaning of implanted CRT device and to predict the response to device implantation, based on cardiac flow analysis.

155 Effects on sacubitril/valsartan on natriuretic peptides in patients with a reduced ejection fraction

Aims The PARADIGM-HF trial proved the superiority of sacubitril/valsartan (Sa/Va) vs. enalapril in reducing mortality and hospitalization for heart failure (HF). Sacubitril/valsartan, new drug used in treatment of heart failure with reduced systolic function (HFrEF) has recently been shown to improve tolerance to exercise and cardiovascular performance. Methods and results We prospectively enrolled 40 outpatient patients with HFrEF with indication for therapy with sacubitril/valsartan and subjected to serial controls with blood tests, echocardiogram before and during gradual optimization of therapy, with the aim of evaluating the effects of the drug on left ventricular remodelling. We studied 40 patients treated with sacubitril/valsartan for at least 3 months. After a mean follow-up of 120 ± 40 days, 95% of patients reached the maximum dose of the drug without major side effects. The ejection fraction increased while end-diastolic and end-systolic volumes of the left ventricle decreased. We also observed a significant reduction in NT-proBNP values without significant worsening of renal function or hyperkalaemia. There NYHA functional class has improved with a positive impact on the prognosis of heart failure at 2 years (P = 0.006). Conclusions In our population, medium-term treatment with sacubitril/valsartan demonstrated a favourable effect on left ventricular remodelling and functional status, confirming the data of previous clinical trials in real life. One more follow-up long and a larger population will help confirm these to confirm these positive effects of the drug on patients with HfrEF.

Ventricular-arterial coupling changes as an early predictor of left ventricular remodelling in atrial fibrillation

Objective Atrial fibrillation (AF) can be associated with adverse atrial and ventricular remodelling also in the absence of persistently elevated heart rate. Ventricular–arterial coupling (VAC) plays a pivotal role in cardiac and aortic adaptation to pathophysiological conditions. The aim of this study was to investigate changes in conventional and novel VAC indexes in long lasting paroxysmal AF. Methods Participants with paroxysmal AF, in sinus rhythm on admission, with preserved left ventricle (LV) systolic function and carotid – femoral pulse wave velocity (PWV) within normal range were carefully selected from consecutive patients admitted to University Hospital in Krakow for scheduled AF ablation. We excluded those with established coronary artery disease, moderate or severe heart valves disease, with uncontrolled hypertension or other comorbidities. The anthropometric and demographic data, medical history, and habits were collected using standardized questionnaire. A total of 51 (mean age 57.7 yrs; 37 men) patients underwent simultaneous echocardiographic and arterial data acquisition. End-systolic pressure was determined from central pulse wave analyses. Arterial elastance (Ea) and LV elastance (Ees) were calculated as end-systolic pressure/stroke volume and end-systolic pressure/end-systolic volume. Two-dimensional speckle tracking was used to derive LV global longitudinal strain (GLS), and then PWV to GLS ratio was calculated. Results Patient presented moderate (EHRA class median = 2b) and long-lasting symptoms (median of AF history 3 years). There was an association of Ees (parameter estimate (PE) 0.12; P=0.0004) and VAC (Ea/Ees) (PE=−0.13; P=0.33) with duration of AF history in the univariate linear regression model and this association retain statistically significant in a model including age, sex, history of hypertension and hypercholesterolemia. Longer history of AF was related to lower PWV to GLS ratio, however this association reached statistical significance only among patients with AF lasting more than 3 years (PE=−0.14; P=0.024) and persisted significant after accounting for covariates. Conclusion The relationship between AF and LV dysfunction is complex and potentially bi-directional. Paroxysmal AF however, can contribute to abnormality in heart–vessel coupling, even when LV function remained within the normal range, indicating early stage of ventricular remodelling due to arrythmia. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Collegium Medicum, Jagiellonian University, Krakow

Prediction of early left ventricular recovery and adverse remodelling in patients with acute myocardial infarction: the role of non-invasive myocardial work evaluation

Background Left ventricular recovery (LVR) and adverse left ventricular remodelling (aLVR) after acute myocardial infarction (AMI) play an important prognostic role. Purpose Our aim was to evaluate the usefulness of non-invasive myocardial work (MW), a new index of global and regional myocardial performance, to predict LVR and aLVR. Methods Fifty patients with AMI (mean age, 63,8±13,4 years), treated by percutaneous coronary intervention (PCI), were prospectively enrolled and underwent a transthoracic Doppler echocardiography within 48 hours after PCI and a median of 31 days at follow-up. Myocardial work is derived from the strain-pressure relation, integrating in its calculation the non-invasive arterial pressure. Segmental LVR was defined as an absolute improvement of left ventricular ejection fraction (LVEF) ≥5% from LVEF at the baseline. The aLVR was defined as an increase of ≥20% of the LV end diastolic volume (LVEDV) at 1 month follow up. Results We found significant differences between the baseline and the follow-up value of LVEF (49,28 vs 52,80 p=0.001), Global Longitudinal Strain (GLS) (−13,41 vs −18,72, p=0.016), Global Work Index (GWI) (1368,68 vs 1788,08, p<0.0001), Global Work Efficiency (GWE) (86,96 vs 91,36, p=0.001), and Global Constructive Work (GCW) (1619,16 vs 2008,68, p<0.0001). The LVR at 1 month of follow-up was observed in 36% of the population enrolled, whereas aLVR was described in 18% of cases. Using ROC curve analysis, we identified a cut off value of 137 mmHg/% for baseline Global Wasted Work (Sensitivity 100%, Specificity 57,14%, AUC 0.6667, CI 95%: 0,51618- 0,81715, p<0.0001) to identify patients with aLVR at 1 month. With regards to conventional echo parameters, patients with LVR showed lower baseline Wall Motion Score Index (WMSI) than those with LVR (1,73 vs 1,38, p=0.007). Conclusions Baseline global wasted work can predict early adverse left ventricular remodelling at 1 months after AMI. These parameters could be used at baseline in order to predict worse outcome in AMI patients. Further larger scale studies are needed to validate these findings. FUNDunding Acknowledgement Type of funding sources: None.

Effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on left ventricular remodelling and longitudinal strain: a prospective observational study

Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) lower cardiovascular events in type 2 diabetes mellitus (T2DM) patients, although the mechanisms underlying these benefits are not clearly understood. Our aim was to study the effects of SGLT2i on left ventricular remodelling and longitudinal strain. Methods Between November 2019 and April 2020, we included 52 patients with T2DM ≥ 18 years old, with HbA1c between 6.5 and 10.0%, and estimated glomerular filtration ≥ 45 ml/min/1.73 m2. Patients were classified into SGLT2i group and control group, according to prescribed treatment by their referring physician. Conventional and speckle tracking echocardiography were performed by blinded sonographers, at baseline and after 6 months of treatment. Results Among the 52 included patients (44% females, mean age 66.8 ± 8.6 years, mean HbA1c was 7.40 ± 0.7%), 30 patients were prescribed SGLT2i and 22 patients were classified as control group. Mean change in indexed left ventricular mass (LVM) was − 0.85 ± 3.31 g/m2 (p = 0.003) in the SGLT2i group, and + 2.34 ± 4.13 g/m2 (p = 0.58) in the control group. Absolute value of Global Longitudinal Strain (GLS) increased by a mean of 1.29 ± 0.47 (p = 0.011) in the SGLT2i group, and 0.40 ± 0.62 (p = 0.34) in the control group. We did not find correlations between changes in LVM and GLS, and other variables like change in HbA1c. Conclusions Among patients with T2DM, SGLT2i were associated with a significant reduction in indexed LVM and a significant increment in longitudinal strain measured by speckle tracking echocardiography, which may explain in part the clinical benefits found in clinical trials.

Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model

To identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5–6 weeks post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. Early LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories, 21 of which correlated with LV equatorial circumferential strain rate. The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2, and secreted frizzled-related protein 1 (sFRP1). This study shows that early changes in regional peak ACS persist at 5–6 weeks post-MI, when early LVR is observed along with increased tissue levels of D-3PGDH and sFRP1. More studies are needed to ascertain if the observed increase in tissue levels of D-3PGDH and sFRP1 might be casually involved in the pathogenesis of adverse LV remodelling.