Left Ventricular Cardiac Function Research Articles

HAEMODYNAMIC FORCES ANALYSIS IN PATIENTS WITH PARAVALVULAR REGURGITATION AFTER TAVR: A PROPENSITY–SCORE MATCHED RETROSPECTIVE STUDY

Abstract Background Paravalvular regurgitation (PVR) after TAVR is a frequent complication, but its direct quantification and grading with conventional echocardiography is still limited by several factors. LV remodeling has still a role in the evaluation of PVR and its pathophysiology. Hemodynamic forces (HDF) analysis has emerged as a new tool to evaluate LV cardiac function in addiction to ejection fraction (EF) and global longitudinal strain (GLS). Aim of the study: To evaluate the difference in pre– and post–TAVR HDF in patients with preserved EF, using a propensity–matched analysis comparing patients with more than mild PVR to patients with mild or no PVR. Medis Ultrasound Suite software has been used for the estimation of HDF in order to differentiate earlier LV function modification between the two groups and its relationship with clinical outcomes. Material and Methods 25 patients from two European high–volume centers with more than mild PVR and coupled pre– and post–TAVR echocardiographic evaluation available for HDF analysis were retrospectively included, paired 1:2 with 50 patients, matched for characteristics that may influence HDF analysis and with mild or none PVR. Clinical outcome was a composite of heart failure (HF) valve–related hospitalization and worsening HF at 1 year. Results No significative differences were found at baseline clinical and echocardiography evaluation between the two groups: median age was 83 years, mean LVEF was 61%. Post–procedural echocardiographic evaluation was performed at 34 days after TAVR (IQR 5 – 50). Patients with significant PVR had higher LV end–diastolic volume (p = 0.044), lower endocardial GLS (p = 0.07) and lower LV diastolic apex–base longitudinal forces (LVD Apex–Base) (p = 0.045). The difference between LVD Apex–base pre– and post–TAVR was significantly lower in the significant PVR group (–0.8 vs 0.3%, p = 0.021). At Cox regression analysis, LV longitudinal force (LVLF) Ratio turned out to be predictive of clinical outcome (HR 1.11, 95CI 1.02 – 1.20, p = 0.017) in the overall population. Conclusion HDF analysis seems to be superior to conventional echocardiographic values of left ventricular cardiac function to detect the early effects of LV volume overload in patients with significant PVR after TAVR. Furthermore, in the overall population, LVLF Ratio predicts clinical outcomes and could be a promising new index to better evaluate the development of heart failure in patients with AS undergoing TAVR.

Retrieval of Embolized WATCHMAN® Flex Atrial Appendage Occlusion Device.

This case report documents the management of a 66-year old man with atrial fibrillation with recent placement of a WATCHMAN® Flex atrial appendage occlusion device. The patient presented with renal failure, abdominal pain, and difficulty walking 2months after placement. The WATCHMAN® Flex device was found to have embolized to his abdominal aorta at the level of the renal arteries with associated thrombus. Extensive workup revealed reduced left ventricular cardiac function and decreased renal function, both of which were felt to be potentially reversible with device removal. The patient then underwent retrieval of the device and all associated thrombus via an open retroperitoneal approach. This case demonstrates a potential consequence of implanting devices such as an atrial appendage occlusion device and describes a technique for removal.

Exogenous Thyroxine Normalizes Decreased Heart Rate in Insulin Resistant OLETF Rats

Diabetic cardiomyopathy (DCM) is defined as heart failure in the absence of overt clinical coronary artery disease, valvular disease, hypertension, and dyslipidemia in diabetic patients. Patients with T2DM display left ventricular dysfunction, fibrosis, and abnormal cell signaling leading to diastolic and systolic dysfunction. Increased left ventricular mass and fibrosis potentially leads to abnormal diastolic function. Substantial data exists demonstrating both insulin-dependent and non-insulin dependent diabetes impairs left ventricular function. During insulin resistance, a metabolic shift occurs favoring fatty acid metabolism at the expense of impaired glucose metabolism, leading to lipotoxicity, increased oxidative stress, and inflammation. Thyroid hormones have shown to be cardioprotective. We have previously shown exogenous thyroxine treatment increased GLUT4 translocation and nuclear factor erythroid 2-related factor 2 (Nrf2) in cardiac tissue, demonstrating the potential to improve glucose metabolism and increase antioxidant defense mechanisms. Insulin resistant, Otsuka Long Evans Tokushima Fatty (OLETF) rats were used to assess the effects of exogenous thyroxine (T4) on left ventricular cardiac function and hemodynamics to assess if the previously observed improvements in cellular metabolism translated to functional improvements. Rats were assigned to three groups: (1) lean, Long Evans Tokushima Otsuka (LETO; n=7), (2) untreated OLETF (n=6), and (3) OLETF + T4 (8 μg/100g BM/d × 6 wks, n=7). Left ventricular function was measured by the pressure-volume system. Heart mass increased in untreated OLETF (1.46 ± 0.08) and treated OLETF (1.61 ± 0.16) compared to LETO (1.19 ± 0.08). Cardiac output (CO) and stroke volume were 26% and 56% greater in untreated OLETF compared to LETO. Heart rate (HR) was 27% lesser in untreated OLETF compared to LETO. While exogenous T4 did not alter CO and SV compared to untreated OLETF, it did normalize HR to LETO levels. The differences in CO between LETO and OLETF suggest that elevated T4 alters the mechanisms (SV vs HR) by which CO is elevated during MetS. The changes may be compensatory to accommodate the cardiac hypertrophy observed in the strain. American Heart Association Award # 946746 APS Porter Physiology Development Fellow (2nd year). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

L-carnitine decreases myocardial injury in children undergoing open-heart surgery: A randomized controlled trial

Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. The aim of this study was to study the effect of L-carnitine on myocardial injury in children undergoing open-heart surgery. This clinical trial was performed on 60 children with congenital heart disease (CHD) who underwent open-heart surgery. They were randomized into two groups: L-carnitine group who received L-carnitine 50 mg\\kg\\day once daily for 1 month before cardiac surgery and control group who received placebo for 1 month before cardiac surgery. Left ventricular cardiac function was assessed by conventional echocardiography to measure left ventricular ejection fraction (LVEF) and two-dimensional speckle tracking echocardiography (2D-STE) to determine left ventricular global longitudinal strain (2D-LV GLS). Blood samples were obtained pre-operatively at baseline before the administration of L-carnitine or placebo and 12 h post-operatively to measure the level of malondialdehyde (MDA), superoxide dismutase (SOD), fas, caspase-3, creatinine kinase-MB (CK-MB), and troponin I. L-carnitine group had significantly lower post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I), but they had significantly higher SOD post-operative level compared to the control group. In addition, post-operative LVEF and 2D-LVGLS were significantly lower in the control group compared to L-carnitine group. Conclusion: L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery. Trial registration: The clinical trial was registered at www.pactr.org with registration number PACTR202010570607420 at 29/10/2020 before recruiting the patients.What is Known:• Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes.• L-carnitine was reported to have myocardial protective effects in rheumatic valvular surgery and coronary artery bypass graft (CABG) in adults; however, there is no evidence on its effectiveness in children undergoing open-heart surgery.What is New:• L-carnitine significantly lowered the post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I) in the treatment group.• L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery.

Association between left ventricular remodeling and lipid profiles in obese children: an observational study.

Childhood obesity has become a prominent issue in the society, which can lead to left ventricular remodeling and severe cardiovascular complications in adulthood. It is beneficial to identify the causes of left ventricular remodeling so that targeted measures can be taken to prevent the cardiovascular disease. Therefore, this study aimed to explore the relationship between left ventricular remodeling and changes in blood lipid indexes in obese children. This study was conducted on 40 healthy non-obese children and 140 obese children diagnosed in the pediatric health department of our hospital. Clinical data collected from the two groups were compared. Echocardiography was performed to examine left ventricular configuration and cardiac function. Multiple linear regression analysis was conducted to assess the independent effects of blood lipid levels on echocardiographic parameters. Blood lipid indicators among different left ventricular structural patterns which were classified according to left ventricular mass indexes and relative wall thickness were compared. Obese children exhibited significantly increased height, weight, body mass index (BMI), body fat percentage (BFP), blood pressure, triglycerides, total cholesterol, left ventricular internal diameter (LVIDd), interventricular septum (IVSd), left ventricular posterior wall diastolic thickness (LVPWd), myocardial mass (LVM) and relative wall thickness (RWT), as well as lower high-density lipoprotein cholesterol (HDL-C) and left ventricular ejection fraction (LVEF) compared to the non-obese children (P < 0.05). Multiple linear correlation analysis showed LVM had a significantly positive correlation with BMI (r = 3.21, P = 0.002) and SBP (r = 2.61, P = 0.01); LVMI had a significantly negative correlation with HDL-C (r = -2.45, P = 0.015); RWT had a significantly positive correlation with SBP (r = 2.50, P = 0.013) but a significantly negative correlation with HDL-C (r = -2.35, P = 0.02). Furthermore, there were significant differences in HDL-C values among children with different ventricular configurations (P < 0.05), with the lowest HDL-C value recorded in the concentric hypertrophy group. Obese children will develop left ventricular remodeling. The left ventricular configuration indexes are most significantly associated with serum HDL-C. Lower HDL-C level contributes to severer left ventricular hypertrophy, indicating a concentric hypertrophy pattern.

Gene therapy encoding cell cycle factors to treat chronic ischemic heart failure in rats.

Gene therapies to induce cardiomyocyte (CM) cell cycle re-entry have shown a potential to treat subacute ischaemic heart failure (IHF) but have not been tested in the more relevant setting of chronic IHF. Our group recently showed that polycistronic non-integrating lentivirus encoding Cdk1/CyclinB1 and Cdk4/CyclinD1 (TNNT2-4Fpolycistronic-NIL) is effective in inducing CM cell cycle re-entry and ameliorating subacute IHF models and preventing the subsequent IHF-induced congestions in the liver, kidneys, and lungs in rats and pigs. Here, we aim to test the long-term efficacy of TNNT2-4Fpolycistronic-NIL in a rat model of chronic IHF, a setting that differs pathophysiologically from subacute IHF and has greater clinical relevance. Rats were subjected to a 2-h coronary occlusion followed by reperfusion; 4 weeks later, rats were injected intramyocardially with either TNNT2-4Fpolycistronic-NIL or LacZ-NIL. Four months post-viral injection, TNNT2-4Fpolycistronic-NIL-treated rats showed a significant reduction in scar size and a significant improvement in left ventricular (LV) systolic cardiac function but not in the LV dilatation associated with chronic IHF. A mitosis reporter system developed in our lab showed significant induction of CM mitotic activity in TNNT2-4Fpolycistronic-NIL-treated rats. This study demonstrates, for the first time, that TNNT2-4Fpolycistronic-NIL gene therapy induces CM cell cycle re-entry in chronic IHF and improves LV function, and that this salubrious effect is sustained for at least 4 months. Given the high prevalence of chronic IHF, these results have significant clinical implications for developing a novel treatment for this deadly disease.

FRI607 SGLT2 Inhibition Improves Muscle Oxidative Capacity And Its Relationship With Cardiac Performance In Patients With T2D And Heart Failure

Abstract Disclosure: Y. Qin: None. N.D. Sanchez: None. A.J. Moody: None. F.M. Acosta: None. S. Neppala: None. M. Brown: None. H. Honka: None. B. Todd: None. L.A. Cruz Moreno: None. A.R. Stepanenko: None. S.E. Espinoza: None. N. Musi: None. C. Triplitt: None. G. Clarke: None. E. Cersosimo: None. R.A. DeFronzo: None. C. Solis-Herrera: None. Cardioprotective benefits of SGLT2 inhibitors (SGLT2i) have been largely thought to be coupled to a physiologic increase in plasma ketones, with much interest in the role of adaptive changes in cardiac fuel source in subjects with T2D and HF. Given the changes in the global dynamics of bioenergetics with SGLT2i, and the proven pleiotropic effects of ketone bodies, suggest that, in addition to their cardioprotective function, SGLT2i may influence other organ systems. In particular, how skeletal muscle (SkM), or cardiopulmonary function, respond to these global bioenergetics changes remains largely unknown. A pilot randomized-controlled clinical study was designed to examine the effects of SGLT2i on SkM bioenergetics (31P MRS), &amp; cardiopulmonary function (CPET), and its association with left ventricular cardiac function (MRI). Six subjects (Age=59±2.6, BMI=33.3±1.1, A1c=7.1±0.3) with T2D and HF (&amp;lt;50%) were randomized empagliflozin 25mg/day (SGLT2i) vs. placebo (control) in a 2:1 fashion for 12 weeks. Imaging and clinical evaluations were performed pre- and post-intervention. The SGLT2i group improved EF (28.7 vs. 38.8, p=0.1). SkM 31P MRS at rest, measuring the relative intracellular concentrations of high-energy metabolites of phospholipid breakdown, reduced with SGLT2i, suggesting better energy utilization by the SkM. 31P MRS-after exercise, showed significant improvements in SkM oxidative capacity (KPCR*[PCr], 0.6 to 0.8, p=0.03), with SGLT2i.During CPET testing, the ventilatory anaerobic threshold (VT), with SGLT2i, showed a significant (p=0.05) increase in VT time, suggesting an increase in the time in aerobiosis in these subjects. The minute ventilation-to-carbon dioxide output slope (a strong predictor of cardiopulmonary complications/death) was improved in the SGLT2i group vs. placebo, which could be associated with the CV benefit observed with these agents. Additionally, patient self-reported outcomes (Promis) showed a trend of improvement in the SGLT2i group. In summary, we demonstrate novel and exciting preliminary findings that in patients with T2D &amp; HF, SGLT2i-associated benefits are not isolated to the heart and may also expand to the SkM, including improved oxidative capacity, energy utilization, and SkM recovery post-exercise. With improvements in HF prognostic markers and patient self-reported outcomes. These original findings may represent novel mechanisms contributing to the cardiac benefits of SGLT2i. Presentation: Friday, June 16, 2023

Rivaroxaban, a direct inhibitor of coagulation factor Xa, attenuates adverse cardiac remodeling in rats by regulating the PAR-2 and TGF-β1 signaling pathways.

Factor Xa (FXa) not only plays an active role in the coagulation cascade but also exerts non-hemostatic signaling through the protease-activated receptors (PARs). This study aimed to investigate whether the FXa inhibitor, Rivaroxaban (RIV), attenuates adverse cardiac remodeling in rats with myocardial infarction (MI) and to identify the underlying molecular mechanisms it uses. An MI model was induced in eight-week-old, male Wistar rats, by permanent ligation of the left anterior descending coronary artery. MI rats were randomly assigned to receive RIV or protease-activated receptors 2-antagonist (PAR-2 antagonist, FSLLRY) treatment for four weeks. Histological staining, echocardiography and hemodynamics were used to assess the cardioprotective effects of RIV. Meanwhile, pharmacological approaches of agonist and inhibitor were used to observe the potential pathways in which RIV exerts antifibrotic effects in neonatal rat cardiac fibroblasts (CFs). In addition, real-time PCR and western blot analysis were performed to examine the associated signaling pathways. RIV presented favorable protection of left ventricular (LV) cardiac function in MI rats by significantly reducing myocardial infarct size, ameliorating myocardial pathological damage and improving left ventricular (LV) remodeling. Similar improvements in the PAR-2 antagonist FSLLRY and RIV groups suggested that RIV protects against cardiac dysfunction in MI rats by ameliorating PAR-2 activation. Furthermore, an in vitro model of fibrosis was then generated by applying angiotensin II (Ang II) to neonatal rat cardiac fibroblasts (CFs). Consistent with the findings of the animal experiments, RIV and FSLLRY inhibited the expression of fibrosis markers and suppressed the intracellular upregulation of transforming growth factor β1 (TGFβ1), as well as its downstream Smad2/3 phosphorylation effectors in Ang II-induced fibrosis, and PAR-2 agonist peptide (PAR-2 AP) reversed the inhibition effect of RIV. Our findings demonstrate that RIV attenuates MI-induced cardiac remodeling and improves heart function, partly by inhibiting the activation of the PAR-2 and TGF-β1 signaling pathways.

Inflammation associated with left ventricular hypertrophy in bipolar disorder: A cross-sectional study

ObjectiveInflammation has received increasing attention as a contributor to the pathophysiology of bipolar disorder (BD) and cardiac hypertrophy into heart failure (HF). Accordingly, we chose BD-related inflammatory markers to investigate their relationships with cardiac left ventricular function and structure in BD. MethodsSixty physically healthy and euthymic patients with bipolar I disorder were recruited to compare with 50 healthy normal controls. The echocardiography was performed to estimate left ventricular mass index (LVMI) as a parameter of LV hypertrophy (LVH) and left ventricle ejection fraction (LVEF) as a parameter of systolic function. An LVEF above the normal range (>70%) was defined as a hyperdynamic heart. Participants' levels of inflammatory and atherosclerosis-related parameters were measured. ResultsCompared with normal controls, BD group had significantly higher rates of LVH (63% vs. 42%) and hyperdynamic heart (32% vs. 2%) and higher mean values of LVMI and LVEF. After adjustment for the effects of BMI and age, multiple regression analyses of BD group showed that the peripheral level of interleukin-8 was positively associated with LVMI and the level of soluble tumor necrosis factor receptor 1 (sTNF-R1) was positively associated with LVEF. ConclusionsPatients with BD from young adulthood are likely to have LVH with normal LV function and hyperdynamic heart associated with diastolic dysfunction. Low-grade inflammation may underlie the mechanisms of LV hypertrophy and cardiac dysfunction in BD patients.

The assessment of left ventricular volume and function in gated small animal 18F-FDG PET/CT imaging: a comparative study of three commercially available software tools

BackgroundSeveral software tools have been developed for gated PET imaging that use distinct algorithms to analyze tracer uptake, myocardial perfusion, and left ventricle volumes and function. Studies suggest that different software tools cannot be used interchangeably in humans. In this study, we sought to compare the left ventricular parameters in gated 18F-FDG PET/CT imaging in mice by three commercially available software tools: PMOD, MIM, and QGS.Methods and resultsHealthy mice underwent ECG-gated 18F-FDG imaging using a small-animal nanoPET/CT (Mediso) under isoflurane narcosis. Reconstructed gates PET images were subsequently analyzed in three different software tools, and cardiac volume and function (end-diastolic (EDV), end-systolic volumes (ESV), stroke volume (SV), and ejection fraction (EF)) were evaluated. While cardiac volumes correlated well between PMOD, MIM, and QGS, the left ventricular parameters and cardiac function differed in agreement using Bland–Altman analysis. EDV in PMOD vs. QGS: r = 0.85; p < 0.001, MIM vs. QGS: r = 0.92; p < 0.001, and MIM vs. PMOD: r = 0.88; p < 0.001, showed good correlations. Correlation was also found in ESV: PMOD vs. QGS: r = 0.48; p = 0.07, MIM vs QGS: r = 0.79; p < 0.001, and MIM vs. PMOD: r = 0.69; p < 0.01. SV showed good correlations in: PMOD vs. QGS: r = 0.73; p < 0.01, MIM vs. QGS: r = 0.86; p < 0.001, and MIM vs. PMOD: r = 0.92; p < 0.001. However, EF among correlated poorly: PMOD vs. QGS: r = −0.31; p = 0.26, MIM vs. QGS: r = 0.48; p = 0.07, and MIM vs. PMOD: r = 0.23; p = 0.41. Inter-class and intra-class correlation coefficient were > 0.9 underlining repeatability in using PMOD, MIM, and QGS for cardiac volume and function assessment.ConclusionsAll three commercially available software tools are feasible in small animal cardiac volume assessment in gated 18F-FDG PET/CT imaging. However, due to software-related differences in agreement analysis for cardiac volumes and function, PMOD, MIM, and QGS cannot be used interchangeably in murine research.

Cardiac MRI: An Alternative Method to Determine the Left Ventricular Function

(1) Background: With the conventional contour surface method (KfM) for the evaluation of cardiac function parameters, the papillary muscle is considered to be part of the left ventricular volume. This systematic error can be avoided with a relatively easy-to-implement pixel-based evaluation method (PbM). The objective of this thesis is to compare the KfM and the PbM with regard to their difference due to papillary muscle volume exclusion. (2) Material and Methods: In the retrospective study, 191 cardiac-MR image data sets (126 male, 65 female; median age 51 years; age distribution 20-75 years) were analysed. The left ventricular function parameters: end-systolic volume (ESV), end-diastolic volume (EDV), ejection fraction (EF) and stroke volume (SV) were determined using classical KfW (syngo.via and cvi42 = gold standard) and PbM. Papillary muscle volume was calculated and segmented automatically via cvi42. The time required for evaluation with the PbM was collected. (3) Results: The size of EDV was 177 mL (69-444.5 mL) [average, [minimum-maximum]], ESV was 87 mL (20-361.4 mL), SV was 88 mL and EF was 50% (13-80%) in the pixel-based evaluation. The corresponding values with cvi42 were EDV 193 mL (89-476 mL), ESV 101 mL (34-411 mL), SV 90 mL and EF 45% (12-73%) and syngo.via: EDV 188 mL (74-447 mL), ESV 99 mL (29-358 mL), SV 89 mL (27-176 mL) and EF 47% (13-84%). The comparison between the PbM and KfM showed a negative difference for end-diastolic volume, a negative difference for end-systolic volume and a positive difference for ejection fraction. No difference was seen in stroke volume. The mean papillary muscle volume was calculated to be 14.2 mL. The evaluation with PbM took an average of 2:02 min. (4) Conclusion: PbM is easy and fast to perform for the determination of left ventricular cardiac function. It provides comparable results to the established disc/contour area method in terms of stroke volume and measures "true" left ventricular cardiac function while omitting the papillary muscles. This results in an average 6% higher ejection fraction, which can have a significant influence on therapy decisions.

Dose titration of sacubitril/valsartan for heart failure with reduced ejection fraction: a real-world study.

The study aims to explore the real-world titration patterns of sacubitril/valsartan in a chronic heart failure (HF) follow-up management system and the effect on the recovery of ventricular remodelling and cardiac function in China. This is a single-centre, observational study of 153 adult outpatients with HF and reduced ejection fraction who were managed in the chronic HF follow-up management system and prescribed with sacubitril/valsartan from August 2017 to August 2021 in China. All patients tried to titrated sacubitril/valsartan to the tolerant dose during follow-up. The primary outcome was the proportion of patients who reached and maintained the target dose of sacubitril/valsartan. The main secondary outcomes were the changes in left atrium diameter, left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) from baseline to 12months. Among the patients, 69.3% were male, with a median age of 49years. The baseline systolic blood pressure (SBP) was 117.6±18.3mmHg before starting the treatment of sacubitril/valsartan. Benefiting from the management system, 117 (76.5%) patients achieved the target dose of sacubitril/valsartan, and the median time to reach the target dose was 3 (IQR 1-5) months. Advanced age and lower SBP may be predictors of failure to reach the target dose. Compared with baseline, standard treatment resulted in a pronounced improvement in left ventricular geometry and cardiac function. The patients showed a significant increase in LVEF [28 (IQR 21-34) % vs. 42 (IQR 37.0-54.3) %, P<0.001], with a great reduction in left atrium diameter [45 (IQR 40.3-51.0) mm vs. 41 (IQR 37.0-45.3) mm, P<0.001] and LVEDD [65 (IQR 60.0-70.3) mm vs. 55 (IQR 52-62) mm, P<0.001] during 12month follow-up. Of patients, 36.5% had a LVEF ≥50%, 54.1% had LVEF >40%, and 81.1% experienced an increase in LVEF of ≥10%. After 12month follow-up, the proportion of patients with New York Heart Association classification I or II increased from 41.8% to 96.4%. Additionally, there was a significant improvement in N-terminal pro-B-type natriuretic peptide (P<0.001). At Month 12, 50% of patients achieved the target dose of beta-blockers. No serious adverse events caused by sacubitril/valsartan were observed during the follow-up. Optimising HF follow-up management was essential and effective in a real-world clinical setting; the majority could reach the target dose of sacubitril/valsartan within the management system and achieve a remarkable improvement in cardiac function and ventricular remodelling.

Magnesium Improves Cardiac Function in Experimental Uremia by Altering Cardiac Elastin Protein Content.

Cardiovascular complications are accompanied by life-threatening complications and represent the major cause of death in patients with chronic kidney disease (CKD). Magnesium is important for the physiology of cardiac function, and its deficiency is common in CKD. In the present study, we investigated the impact of oral magnesium carbonate supplementation on cardiac function in an experimental model of CKD induced in Wistar rats by an adenine diet. Echocardiographic analyses revealed restoration of impaired left ventricular cardiac function in animals with CKD. Cardiac histology and real-time PCR confirmed a high amount of elastin protein and increased collagen III expression in CKD rats supplemented with dietary magnesium as compared with CKD controls. Both structural proteins are crucial in maintaining cardiac health and physiology. Aortic calcium content increased in CKD as compared with tissue from control animals. Magnesium supplementation numerically lowered the increases in aortic calcium content as it remained statistically unchanged, compared with controls. In summary, the present study provides evidence for an improvement in cardiovascular function and aortic wall integrity in a rat model of CKD by magnesium, as evidenced by echocardiography and histology.

Minocycline pre-treatment up-regulates antioxidant enzymes and enhances the regenerative potential of MSCs in rat myocardial infarction model.

To determine the effect of the pre-treatment of mesenchymal stem cells (MSCs) with minocycline on the expression of antioxidant genes and cardiac repair post myocardial infarction (MI) in rats. Rat bone marrow derived MSCs were used in the study. Cytotoxicity of minocycline in MSCs was determined using JC1 assay to identify a safe drug dose for further experiments. The MSCs were pre-treated with 1.0 µM minocycline for 24 hours and then treated with hydrogen peroxide (H2O2), after that mRNA was isolated and the expression levels of antioxidant genes including peroxiredoxin, glutathione peroxidase, and superoxide dismutase were determined. Finally, minocycline pre-treated MSCs were used to treat rats induced with MI by the ligation of left anterior descending coronary artery. The cardiac function was evaluated at two and four weeks post MI using echocardiography. At 1.0 µM concentration, minocycline was found to be safe for MSCs and used for subsequent experiments. Minocycline pre-treatment was found to up regulate several antioxidant genes in oxidatively stressed MSCs. Furthermore, minocycline pre-treated MSCs displayed greater improvement in cardiac left ventricular function at two and four-weeks post MI as compared to untreated rats. Pre-treatment of MSCs with minocycline enhances the expression of antioxidant genes and promotes their capability to repair cardiac function after MI.

PS-BPB02-4: LEFT VENTRICLE HYPERTROPHY AND DYSFUNCTION WERE EXAGGERATED BY P2RX7 KNOCKOUT BUT UNAFFECTED BY P2RX7 PHARMACOLOGIC BLOCKADE IN ANGIOTENSIN II-INFUSED MICE

Objective: Extracellular adenosine triphosphate released from damaged cells binds to the P2X7 receptor (P2RX7) to activate of immune cells. Our preliminary data demonstrated that P2RX7 plays a role in vascular injury of hypertensive mice. Angiotensin (Ang) II-induced hypertension, vascular injury and aortic perivascular infiltration of activated T cell were attenuated by P2rx7 knockout or P2RX7 pharmacologic blockade. However, whether P2RX7 is involved in Ang II-induced cardiac dysfunction and hypertrophy is unknown. We hypothesized that Ang II-induced left ventricular (LV) dysfunction and hypertrophy would be blunted by P2rx7 knockout or P2RX7 antagonism. Design and method: Ten-to-12-week-old male C57BL/6J wild-type (WT) and P2rx7-/- mice were infused or not with Ang II (1000 ng/kg/min) for 14 days. A second set of Ang II-infused WT mice was infused with the P2RX7 antagonist AZ10606120 (694 ng/kg/min) or vehicle for 14 days. Cardiac LV function and remodeling were determined by ultrasound. Total RNA was isolated from the heart using the mirVana miRNA isolation kit. Relative expression was calculated using the Pfaffl method with 40S ribosomal protein S16 (Rps16) as a reference gene. Hypertrophic and fibrotic markers were studied by reverse transcription-quantitative PCR (RT-qPCR) in cardiac ventricles. Results: Ang II-induced 1.5-fold increase in LV mass/body weight (P &lt; 0.001) and ∽25% decrease in fractional shortening in WT mice and mice receiving AZ10606120 (P &lt; 0.05). These changes were exaggerated in P2rx7-/- mice (LV mass/body weight: 1.7-fold increase, fractional shortening: 54% decrease, P &lt; 0.05), but not in mice receiving AZ10606120. Ang II-induced atrial natriuretic peptide (Nppa/Rps16: 7-fold, P &lt; 0.001) and α-skeletal actin 1 expression (Acta1/Rps16: 6-fold, P &lt; 0.001) tended to be further increased in P2rx7-/- mice (Nppa/Rps16: 14-fold and Acta1/Rps16: 12-fold), but not in AZ10606120-treated mice. Ang II-induced myosin heavy chain 7B (14-fold, P &lt; 0.05) was unaffected by P2rx7 knockout or P2RX7 antagonism. Ang II caused a 1.5-fold increase in transforming growth factor β; 1 only in P2rx7-/- mice (P &lt; 0.05). Conclusion: Ang II-induced LV hypertrophy and dysfunction were exaggerated by P2rx7 knockout but were not affected by P2RX7 pharmacologic blockade.

Ameliorative Effects of Cang-ai Volatile Oil on Left Ventricular Remodeling in Rats

To evaluate with 7T cardiac magnetic resonance tissue tracking imaging (CMR-TT) the ameliorative effect of Cang-ai volatile oil (CAVO) on left ventricular remodeling (LVR) in rats induced by isoproterenol (ISO), and to make preliminary investigation into CAVO's effects on endothelial dysfunction in LVR. A total of 35 healthy male Sprague-Dawley (SD) rats were randomly assigned to two groups, the experimental group ( n=27) and the normal control group ( n=8). The rat model of LVR was established by subcutaneous injection of ISO solution at 10 mg·kg -1·d -1 at multiple sites for 10 consecutive days. After modeling was completed, the surviving rats ( n=24) in the experimental group were then randomly assigned to the blank experimental group, CAVO group, and Shexiang Baoxin pill (SXBXP) group ( n=8 in each group). Rats in each group were given via gavage the corresponding intervention medicine or an equivalent amount of normal saline solution for 28 consecutive days. At the end of modeling and intragastric intervention, 7T CMR cine sequence scanning was conducted to collect data. Then, post-processing software CVI42 was used to analyze the images and to compare and contrast the changes in the parameters of left ventricular cardiac function and myocardial strain in each group before and after the administration of the medication. The rats were sacrificed after MRI scanning, and their hearts were harvested for pathological examination. The levels of serum biochemical indicators were measured by enzyme-linked immunosorbent assay (ELISA). CAVO significantly increased LV ejection fraction and overall myocardial strain parameters in LVR rats, while it decreased LV volume, mass, and serum levels of endothelial function indicators in LVR rats. In addition, pathological staining showed marked improvements in the hypertrophy, necrosis and interstitial fibrosis of cardiomyocytes. Through the regulation of myocardial vascular endothelial function, CAVO can significantly improve cardiac functions in LVR rats, delay the process of ventricular remodeling, and have a certain amount of protective effect on cardiac structure and function in rats.

Exercise Training Does Not Attenuate Cardiac Atrophy or Loss of Function in Individuals With Acute Spinal Cord Injury: A Pilot Study

ObjectiveTo investigate the effects of 2 modes of exercise training, upper-body alone, and the addition of electrical stimulation of the lower body, to attenuate cardiac atrophy and loss of function in individuals with acute spinal cord injury (SCI). DesignRandomized controlled trial. SettingRehabilitation Hospital. ParticipantsVolunteers (N=27; 5 women, 22 men) who were <24 months post SCI. InterventionsVolunteers completed either 6 months of no structured exercise (Control), arm rowing (AO), or a combination of arm rowing with electrical stimulation of lower body paralyzed muscle (functional electrical stimulation [FES] rowing). Main Outcome MeasuresTransthoracic echocardiography was performed on each subject prior to and 6 months after the intervention. The relations between time since injury and exercise type to cardiac structure and function were assessed via 2-way repeated-measures analysis of variance and with multilevel linear regression. ResultsTime since injury was significantly associated with a continuous decline in cardiac structure and systolic function, specifically, a reduction in left ventricular mass (0.197 g/month; P=.049), internal diameter during systole (0.255 mm/month; P<.001), and diastole (0.217 mm/month; P=.019), as well as cardiac output (0.048 L/month, P=.019), and left ventricular percent shortening (0.256 %/month; P=.027). These associations were not differentially affected by exercise (Control vs AO vs FES, P>.05). ConclusionsThese results indicate that within the subacute phase of recovery from SCI there is a linear loss of left ventricular cardiac structure and systolic function that is not attenuated by current rehabilitative aerobic exercise practices. Reductions in cardiac structure and function may increase the risk of cardiovascular disease in individuals with SCI and warrants further interventions to prevent cardiac decline.

A retrospective study: do patients with left ventricular ejection fraction ≤50% benefit from heart valve surgery?

Left ventricular ejection fraction (LVEF) is an indicator of heart failure, and it is controversial whether patients with reduced preoperative left ventricular ejection fraction can benefit from heart valve surgery. We aimed to assess the differences in clinical characteristics after surgery in patients with different grades of reduced preoperative LVEF to guide clinical management. A total of 100 heart valve disease patients with low LVEF (≤50%) who had undergone valve surgery in the Department of Cardiology. The patients were divided into three groups according to their LVEF measured by echocardiography before surgery, with LVEF ≤40% as group A, 40%< LVEF ≤45% as group B, and 45%< LVEF ≤50% as group C. Clinical characteristics such as postoperative LVEF values, oxygenation index, liver function and inflammatory index, intra-aortic balloon pump (IABP) utilization rate, and mortality were compared among the three groups of patients. There was no statistically significant difference in the preoperative baseline data between the three groups of patients (P>0.05). The clinical outcomes of patients in group A (n=28) were similar to those of patients in groups B (n=39) and C (n=33) (P>0.05). The vasoactive-inotropic score (VIS), postoperative ventilator use time, length of stay in the care unit, IABP use rate, and mortality rate on the first postoperative day were higher in group A. By comparing the preoperative and postoperative (within 48 hours and 3 months after surgery) cardiac echocardiograms of the three groups, we learned that LVEF increased, LV end-systolic internal diameter and LV end-diastolic internal diameter decreased, and ventricular remodeling improved after surgery compared with the preoperative period (P<0.05). The postoperative improvement was more obvious in group A than in groups B and C. Three months after surgery, LVEF increased to 55%, the LV end-systolic internal diameter decreased to 39 mm, and the LV end-diastolic internal diameter decreased to about 55 mm in each group (P>0.05). Patients with heart valve disease and low LVEF should be actively treated with heart valve surgery, which can significantly improve the patient's left ventricular reverse remodeling and cardiac function, thereby facilitating survival.

A Machine Learning Challenge: Detection of Cardiac Amyloidosis Based on Bi-Atrial and Right Ventricular Strain and Cardiac Function.

This study challenges state-of-the-art cardiac amyloidosis (CA) diagnostics by feeding multi-chamber strain and cardiac function into supervised machine (SVM) learning algorithms. Forty-three CA (32 males; 79 years (IQR 71; 85)), 20 patients with hypertrophic cardiomyopathy (HCM, 10 males; 63.9 years (±7.4)) and 44 healthy controls (CTRL, 23 males; 56.3 years (IQR 52.5; 62.9)) received cardiovascular magnetic resonance imaging. Left atrial, right atrial and right ventricular strain parameters and cardiac function generated a 41-feature matrix for decision tree (DT), k-nearest neighbor (KNN), SVM linear and SVM radial basis function (RBF) kernel algorithm processing. A 10-feature principal component analysis (PCA) was conducted using SVM linear and RBF. Forty-one features resulted in diagnostic accuracies of 87.9% (AUC = 0.960) for SVM linear, 90.9% (0.996; Precision = 94%; Sensitivity = 100%; F1-Score = 97%) using RBF kernel, 84.9% (0.970) for KNN, and 78.8% (0.787) for DT. The 10-feature PCA achieved 78.9% (0.962) via linear SVM and 81.8% (0.996) via RBF SVM. Explained variance presented bi-atrial longitudinal strain and left and right atrial ejection fraction as valuable CA predictors. SVM RBF kernel achieved competitive diagnostic accuracies under supervised conditions. Machine learning of multi-chamber cardiac strain and function may offer novel perspectives for non-contrast clinical decision-support systems in CA diagnostics.

Long-term cardiac adverse effects after modern Hodgkins lymphoma treatment

Abstract Background Hodgkin's lymphoma (HL) frequently affects both children and young adults. Traditional treatment of HL is effective but associated with a life-time prevalence of cardiac disease exceeding 50%. Treatment protocols were modified in 1997 to reduce cardiotoxicity, primarily by reducing both radiation fields and doses. Purpose To assess the long-term impact of the modified treatment protocols on left ventricular cardiac function. Methods HL survivors (n=244) treated with anthracycline-based chemotherapy using modified treatment protocols in 3 centres in Norway between 1997 and 2007 were included in this cross-sectional study. Of these, 130 (53%) also received mediastinal radiotherapy. They were compared to controls recruited from the general population (n=58) matched for age, sex, and risk-factors. Echocardiography was performed in all subjects. Results The participants were on average 46±9 years old and had received treatment on average 17±3 years before examination. Echocardiographic parameters are shown in the table. Reduced left ventricular (LV) ejection fraction (EF) (&amp;lt;52%) was found in 19 HL-survivors and three controls (13% vs. 6%, p=0.24). Reduced LV global longitudinal strain (GLS) (&amp;gt; −18.0%) was found in 41 HL survivors and three controls (25% vs. 6%, p&amp;lt;0.05). There was no difference in prevalence of reduced GLS between HL survivors who received mediastinal radiotherapy and those who did not (26% vs. 24%, p=0.70). Conclusion While a minority of HL survivors did have a slight reduction in longitudinal deformation, the effect was small and importantly, we found no difference in EF between HL survivors treated with modified protocols and controls. Mediastinal radiotherapy did not seem to increase the prevalence of reduced cardiac function in HL survivors. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): South-Eastern Norway Regional Health Authority