Therapeutic Acellular Scaffolds for Limiting Left Ventricular Remodelling-Current Status and Future Directions

Myocardial infarction (MI) is one of the leading causes of heart-related deaths worldwide. Following MI, the hypoxic microenvironment triggers apoptosis, disrupts the extracellular matrix and forms a non-functional scar that leads towards adverse left ventricular (LV) remodelling. If left untreated this eventually leads to heart failure. Besides extensive advancement in medical therapy, complete functional recovery is never accomplished, as the heart possesses limited regenerative ability. In recent decades, the focus has shifted towards tissue engineering and regenerative strategies that provide an attractive option to improve cardiac regeneration, limit adverse LV remodelling and restore function in an infarcted heart. Acellular scaffolds possess attractive features that have made them a promising therapeutic candidate. Their application in infarcted areas has been shown to improve LV remodelling and enhance functional recovery in post-MI hearts. This review will summarise the updates on acellular scaffolds developed and tested in pre-clinical and clinical scenarios in the past five years with a focus on their ability to overcome damage caused by MI. It will also describe how acellular scaffolds alone or in combination with biomolecules have been employed for MI treatment. A better understanding of acellular scaffolds potentialities may guide the development of customised and optimised therapeutic strategies for MI treatment.

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.

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.