Left Ventricular Reverse Remodeling Research Articles

Effect of sodium-glucose cotransporter protein-2 inhibitors on left ventricular hypertrophy in patients with type 2 diabetes: A systematic review and meta-analysis.

This systematic review and meta-analysis was performed to compare the effect of sodium-glucose cotransporter protein-2 inhibitors (SGLT-2i) and placebo on left ventricular hypertrophy (LVH) in patients with type 2 diabetes. Randomized controlled trials (RCTs) comparing the LVH parameters of SGLT-2i to placebo in patients with type 2 diabetes were included. Our primary outcomes were the changes in left ventricular mass (LVM) and left ventricular mass index (LVMI) from baseline to the study endpoint. Secondary outcomes were the changes in left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the ratio of early mitral inflow velocity to atrial inflow velocity (E/A). Summary odds ratios were estimated using a fixed-effect or random-effect model. A total of 11 articles were included. Data were extracted from 11 original studies matching our inclusion criteria. In our meta-analysis, there were significant improvement in LVM (SMD -0.23, 95% CI -0.44 to -0.02, I 2 = 22.6%, p = 0.034), LVMI (SMD -0.25, 95% CI -0.38 to -0.12, I 2 = 0.0%, p = 0.000), LVEDV (SMD -0.19, 95% CI -0.36 to -0.01, I 2 = 62.3%, p = 0.035), and LVESV (SMD -0.21, 95% CI -0.39 to -0.04, I 2 = 32.9%, p = 0.017) in the SGLT-2i group compared with the placebo group. Furthermore, no significant differences were found in LVEF (SMD 0.13, 95% CI 0.00 to 0.26, I 2 = 0.0%, p = 0.050) and E/A (SMD -0.01, 95% CI -0.22 to 0.20, I 2 = 0%, p = 0.908) between the two groups. This meta-analysis confirmed the beneficial effects of SGLT-2i on reversal of left ventricular remodeling. The LVH regression was more pronounced in studies of type 2 diabetes patients receiving SGLT-2i than placebo.

The Association Between On-treatment Ambulatory Central Blood Pressure and Left Ventricular Reverse Remodeling in Heart Failure With Reduced Ejection Fraction.

Compared to office blood pressure (OBP), central blood pressure (CBP) and ambulatory blood pressure (BP) are known to be better markers for predicting cardiovascular events. We evaluated the association between left ventricular reverse remodeling (LVRR) and ambulatory CBP in heart failure with reduced ejection fraction (HFrEF). This study retrospectively analyzed 93 patients who performed ambulatory CBP and brachial BP (BBP) monitoring from 2018 to 2020 within 1 year after diagnosis of HFrEF at a single tertiary center. We analyzed the association between on-treatment ambulatory BPs and LVRR on follow-up echocardiography. The mean age of participants was 59 years; 65.6% were men; mean LVEF was 29%. Ambulatory BP and follow-up echocardiography were done at 143 days (interquartile range [IQR], 64-267) and 454 days (IQR, 281-600) after diagnosis of HF, respectively. Baseline OBP was not different between 2 groups, but ambulatory systolic CBP was significantly higher in the LVRR group than the non-LVRR group (p=0.005). Systolic OBP (odds ratio [OR], 1.029; confidence interval [CI], 1.004-1.055; p=0.026), 24-hour ambulatory systolic CBP (OR, 1.048; CI, 1.015-1.082; p=0.004), and 24-hour ambulatory systolic BBP (OR, 1.049; CI,1.017-1.082; p=0.003) were associated with LVRR. Compared to ambulatory systolic CBP of 110-119 mmHg, 90-99 mmHg showed lower OR for LVRR. Low on-treatment ambulatory systolic CBP was closely related to a lower likelihood of LVRR in HFrEF than the normal range. Ambulatory CBP measured during treatment of patients with HFrEF appears to be useful in predicting outcomes.

Predicting Hospital Readmissions in Patients Receiving Novel-Dose Sacubitril/Valsartan Therapy: A Competing-Risk, Causal Mediation Analysis.

Backgrounds: Our study aimed to identify and predict patients with heart failure (HF) taking novel-dose Sacubitril/Valsartan (S/V) at risk for all-cause readmission, as well as investigate the possible role of left ventricular reverse remodeling (LVRR). Methods and results: There were 464 patients recruited from December 2017 to September 2021 in our hospital with a median follow-up of 660 days (range, 17-1494). Competing risk analysis with Gray's Test showed statistically significant differences in all-cause readmission (p-value< .001) across the three different dose groups. Models 1 and 2 were developed based on the results of univariable competing risk analysis, least absolute shrinkage and selection operator approach, backward stepwise regression, and multivariable competing risk analysis. The internal verification (data-splitting method) indicated that Model 1 had better discrimination, calibration, and clinical utility. The corresponding nomogram showed that patients aged 75 years and above, or taking the lowest-dose S/V (≤50 mg twice a day), or diagnosed with ventricular tachycardia, or valvular heart disease, or chronic obstructive pulmonary disease, or diabetes mellitus were at the highest risk of all-cause readmission. In the causal mediation analysis, LVRR was considered as a critical mediator that negatively affected the difference of novel-dose S/V in readmission. Conclusions: A significant association was detected between novel-dose S/V and all-cause readmission in HF patients, in part negatively mediated by LVRR. The web-based nomogram could provide individual prediction of all-cause readmission in HF patients receiving novel-dose S/V. The effects of different novel-dose S/V are still needed to be explored further in the future.

T1 Map-Based Radiomics for Prediction of Left Ventricular Reverse Remodeling in Patients With Nonischemic Dilated Cardiomyopathy.

This study aimed to develop and validate models using radiomics features on a native T1 map from cardiac magnetic resonance (CMR) to predict left ventricular reverse remodeling (LVRR) in patients with nonischemic dilated cardiomyopathy (NIDCM). Data from 274 patients with NIDCM who underwent CMR imaging with T1 mapping at Severance Hospital between April 2012 and December 2018 were retrospectively reviewed. Radiomic features were extracted from the native T1 maps. LVRR was determined using echocardiography performed ≥ 180 days after the CMR. The radiomics score was generated using the least absolute shrinkage and selection operator logistic regression models. Clinical, clinical + late gadolinium enhancement (LGE), clinical + radiomics, and clinical + LGE + radiomics models were built using a logistic regression method to predict LVRR. For internal validation of the result, bootstrap validation with 1000 resampling iterations was performed, and the optimism-corrected area under the receiver operating characteristic curve (AUC) with 95% confidence interval (CI) was computed. Model performance was compared using AUC with the DeLong test and bootstrap. Among 274 patients, 123 (44.9%) were classified as LVRR-positive and 151 (55.1%) as LVRR-negative. The optimism-corrected AUC of the radiomics model in internal validation with bootstrapping was 0.753 (95% CI, 0.698-0.813). The clinical + radiomics model revealed a higher optimism-corrected AUC than that of the clinical + LGE model (0.794 vs. 0.716; difference, 0.078 [99% CI, 0.003-0.151]). The clinical + LGE + radiomics model significantly improved the prediction of LVRR compared with the clinical + LGE model (optimism-corrected AUC of 0.811 vs. 0.716; difference, 0.095 [99% CI, 0.022-0.139]). The radiomic characteristics extracted from a non-enhanced T1 map may improve the prediction of LVRR and offer added value over traditional LGE in patients with NIDCM. Additional external validation research is required.

PS-C24-10: HAEMODYNAMIC CHARACTERISTICS OF THE HEART BEFORE AND AFTER CRT IN PATIENTS WITH HEART FAILURE

The aim of the study: to evaluate the clinical and hemodynamic effects of resynchronization therapy in patients with congestive heart failure. Materials and Methods: seventy-six consecutive patients underwent echocardiography, NYHA classification, 6-minute walk test before and after cardiac resynchronization therapy. All had complete left bundle branch block, with a QRS complex duration greater than 130 ms. and left ventricular ejection fraction less than 35%. Also, all patients had received optimal medical therapy for at least 3 months before inclusion to the study. Results: we observed significant increase in left ventricular ejection fraction (on 35.4 ± 3.7%, p &lt; 0.001, compared with baseline) and decrease in end-systolic volume of the left ventricle (on 20.2 ± 3.0%, p &lt; 0.001 compared with baseline). Improvement in functional class of congestive heart failure by NYHA classification by more than 1 was observed in 68.4% of individuals, in 26.3% of participants demonstrated no change and 5.3% of patients had worsening of CHF symptoms. Conclusions: the response of patients with congestive heart failure to cardiac resynchronization therapy is heterogeneous. The relationship between left ventricular reverse remodeling and the functional class of the congestive heart failure was not significant.

Prevalence of early and late left ventricular reverse remodeling in dilated cardiomyopathy under optimal medical therapy

Prevalence of early and late left ventricular reverse remodeling in dilated cardiomyopathy under optimal medical therapy

Modified Glasgow Prognostıc Score May Be Useful to Predict Major Adverse Cardiac Events in Heart Failure Patients Undergone Cardiac Resynchronization Treatment.

Whether modified Glasgow prognostic score predicts prognosis in patients with cardiac resynchronization therapy with defibrillation is unknown. Our aim was to investigate the association of modified Glasgow prognostic score with death and hospitalization in cardiac resynchronization therapy with defibrillation patients. A total of 306 heart failure with reduced ejection fraction patients who underwent cardiac resynchronization therapy with defibrillation implantation were categorized into 3 groups based on their modified Glasgow prognostic score categorical levels. C-reactive protein >10 mg/L or albumin <35 g/L was assigned 1 point each and the patients were classified into 0, 1, and 2 points, respectively. Remodeling was determined according to the clinical event and myocardial remodeling criteria. Major adverse cardiac events were defined as mortality and/or hospitalization for heart failure. Age, New York Heart Association functional class, modified Glasgow prognostic score prior to cardiac resynchronization therapy with defibrillation, sodium levels, and left atrial diameter were higher in the major adverse cardiac events(+) group. Age, left atrial diameter, and higher modified Glasgow prognostic score were found to be predictors of heart failure hospitalization/death in multivariable penalized Cox regression analysis. Besides, patients with lower modified Glasgow prognostic score showed better reverse left ventricular remodeling demonstrated by increase in left ventricle ejection fraction and decline in left ventricle end systolic volume. Modified Glasgow prognostic score prior to cardiac resynchronization therapy with defibrillation can be used as a predictor of long-term heart failure hospitalization and death in addition to age and left atrial diameter. These results can guide the patient selection for cardiac resynchronization therapy with defibrillation therapy and highlight the importance of nutritional status.

Temporal Changes in Extracellular Vesicle Hemostatic Protein Composition Predict Favourable Left Ventricular Remodeling after Acute Myocardial Infarction.

The subset of plasma extracellular vesicles (EVs) that coprecipitate with low-density lipoprotein (LDL-EVs) carry coagulation and fibrinolysis pathway proteins as cargo. We investigated the association between LDL-EV hemostatic/fibrinolysis protein ratios and post-acute myocardial infarction (post-AMI) left ventricular (LV) remodeling which precedes heart failure. Protein concentrations of von Willebrand factor (VWF), SerpinC1 and plasminogen were determined in LDL-EVs extracted from plasma samples obtained at baseline (within 72 h post-AMI), 1 month and 6 months post-AMI from 198 patients. Patients were categorized as exhibiting adverse (n = 98) or reverse (n = 100) LV remodeling based on changes in LV end-systolic volume (increased or decreased ≥15) over a 6-month period. Multiple level longitudinal data analysis with structural equation (ML-SEM) model was used to assess predictive value for LV remodeling independent of baseline differences. At baseline, protein levels of VWF, SerpinC1 and plasminogen in LDL-EVs did not differ between patients with adverse versus reverse LV remodeling. At 1 month post-AMI, protein levels of VWF and SerpinC1 decreased whilst plasminogen increased in patients with adverse LV remodeling. In contrast, VWF and plasminogen decreased whilst SerpinC1 remained unchanged in patients with reverse LV remodeling. Overall, compared with patients with adverse LV remodeling, higher levels of SerpinC1 and VWF but lower levels of plasminogen resulted in higher ratios of VWF:Plasminogen and SerpinC1:Plasminogen at both 1 month and 6 months post-AMI in patients with reverse LV remodeling. More importantly, ratios VWF:Plasminogen (AUC = 0.674) and SerpinC1:Plasminogen (AUC = 0.712) displayed markedly better prognostic power than NT-proBNP (AUC = 0.384), troponin-I (AUC = 0.467) or troponin-T (AUC = 0.389) (p < 0.001) to predict reverse LV remodeling post-AMI. Temporal changes in the ratios of coagulation to fibrinolysis pathway proteins in LDL-EVs outperform current standard plasma biomarkers in predicting post-AMI reverse LV remodeling. Our findings may provide clinical cues to uncover the cellular mechanisms underpinning post-AMI reverse LV remodeling.

Impact of bicuspid aortic valve or tricuspid aortic valve on hemodynamics and left ventricular reverse remodeling in patients after transcatheter aortic valve replacement

Objective: To compare the impact of bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) on hemodynamics and left ventricular reverse remodeling after transcatheter aortic valve replacement (TAVR). Methods: We retrospectively analyzed the clinical data of patients who underwent TAVR in our hospital from January 2019 to March 2021. Patients were divided into BAV group and TAV group according to aortic contrast-enhanced CT. Each patient was followed up by N-terminal pro B-type natriuretic peptide (NT-proBNP) and echocardiography at four time points, namely before TAVR, 24 hours, 1 month and 6 months after TAVR. Echocardiographic data, including mean pressure gradient (MPG), aortic valve area (AVA), left ventricular ejection fraction (LVEF), left ventricle mass (LVM) and LV mass index (LVMi) were evaluated. Results: A total of 41 patients were included. The age was (75.0±8.6) years, and male patients accounted for 53.7%. There were 19 BAV patients and 22 TAV patients in this cohort. All patients undergoing TAVR using a self-expandable prosthesis Venus-A valve. MPG was (54.16±21.22) mmHg(1 mmHg=0.133 kPa) before TAVR, (21.11±9.04) mmHg at 24 hours after TAVR, (18.84±7.37) mmHg at 1 month after TAVR, (17.68±6.04) mmHg at 6 months after TAVR in BAV group. LVEF was (50.42±13.30)% before TAVR, (53.84±10.59)% at 24 hours after TAVR, (55.68±8.71)% at 1 month after TAVR and (57.42±7.78)% at 6 months after TAVR in BAV group. MPG and LVEF substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05) in BAV group. MPG in TAV group improved at each time point after operation, and the difference was statistically significant (all P<0.05). LVMi was (164.13±49.53), (156.37±39.11), (146.65±38.84) and (134.13±39.83) g/m2 at the 4 time points and the value was significantly reduced at 1 and 6 months post TAVR compared to preoperative level(both P<0.05). LVEF in the TAV group remained unchanged at 24 hours after operation, but it was improved at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). LVMi in TAV group substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05). NT-proBNP in both two groups improved after operation, at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). MPG in TAV group improved better than in BAV group during the postoperative follow-up (24 hours after TAVR: (11.68±5.09) mmHg vs. (21.11±9.04) mmHg, P<0.001, 1 month after TAVR: (10.82±3.71) mmHg vs. (18.84±7.37) mmHg, P<0.001, 6 months after TAVR: (12.36±4.42) mmHg vs. (17.68±6.04) mmHg, P=0.003). There was no significant difference in NT-proBNP between BAV group and TAV group at each time point after operation (all P>0.05). There was no significant difference in paravalvular regurgitation and second prosthesis implantation between the two groups (all P>0.05). Conclusions: AS patients with BAV or TAV experience hemodynamic improvement and obvious left ventricular reverse remodeling after TAVR, and the therapeutic effects of TAVR are similar between BAV and TAV AS patients in the short-term post TAVR.

Lung diffusion capacity correlates with pre-implant pulmonary hypertension and predicts outcome after LVAD implantation.

Diffusing capacity of the lung for carbon monoxide (DLCO ) reduction is common in heart failure (HF) and is associated with a worse prognosis. Correlations between DLCO and pulmonary hypertension (PH) are unclear, and published data are conflicting; it has been shown that DLCO impairment may persist or even worsen after normalization of pulmonary pressures following left ventricle assist device (LVAD) implantation, maybe reflecting persistent pulmonary damage. We aimed to investigate the impact of pre-implant DLCO and central haemodynamics on outcome in patients with advanced HF implanted with a LVAD. We retrospectively analysed pre-implant and post-implant data from 42 patients implanted with a LVAD at our institution. Out of 42 patients, 35 had post-capillary PH before implantation, including 17 with combined post- and pre-capillary PH (Cpc-PH). Median DLCO was 59% (IQR 47-68%), and it inversely correlated with pulmonary vascular resistance (PVR) (P 0.037) and diastolic pulmonary gradient (DPG) (P 0.042). Compared with baseline, LVAD resulted in improvement in LV diameter (LVDd, P<0.001), mitral regurgitation (P 0.022), and PH (mPAP 24 vs. 36mmHg, P<0.001; PAWP 12 vs. 23mmHg, P 0.001; pulmonary artery compliance, CPA 3.1 vs. 1.9mL/mmHg, P 0.021). Lower DLCO and Cpc-PH at baseline were associated with a better LV reverse remodelling post-implantation (P 0.027 for LVDd) but also with a smaller gain in CPA (P 0.049). Before LVAD implantation, DLCO impairment is associated with higher PVR and DPG, suggesting that it might be an expression of persistent pulmonary damage occurring in Cpc-PH. After LVAD implantation, both LV dimension and haemodynamics improve. Lower pre-implant DLCO is associated with better LV reverse remodelling.

556 EFFECT OF SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITION ON RIGHT VENTRICULAR FUNCTION IN HEART FAILURE WITH REDUCED EJECTION FRACTION

Abstract Background Sodium-glucose-transporter (SGLT2)-inhibitors have modified heart failure's prognosis since they are able to reduce the combined risk of cardiovascular death or hospitalization for heart failure. Evidence is available about the contribute of these drugs to LV reverse remodeling. Instead, despite the right ventricular disfunction is often related to the left ventricular one, little is known about the effects of SGLT2-inhibitors on right ventricular function. Methods Between October 2021 and February 2022, we enrolled 43 consecutive patients affected by heart failure with reduced ejection fraction on optimal medical therapy including ARNI who initiated SGLT2i therapy. All patients referred to our Heart Failure Clinic and were included in our heart failure registry approved by the local ethical committee A transthoracic echocardiography was performed at the beginning of treatment and after 6 months, evaluating left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVi) and tricuspid annular plane systolic excursion (TAPSE). Right ventricular longitudinal strain (RVLS) was assessed in 27 patients, while 16 were excluded for poor acoustic window. Continuous variables are reported as median and interquartile range and compared with the Mann-Whitney U test as appropriate. Statistical analysis was performed with SPSS version 26 (IBM, Armonk, NY). Results Median age of the study population was 65,8 years [IQR 56,4-75,1]. Median LVEF was 30% [IQR 24-33]. No other medical or electrical therapies for heart failure were introduced during the study period in this population. There was a significant increase of LVEF (30 [24-33] vs 33 [26-40], p 0.001) and a trend toward decrease of LVEDVi (110 [77.5-127] vs 94.7 [67.7-114.6], p 0.084). Moreover, there were no variations of TAPSE (17.5 [16-20] vs 18 [14 to 19.7], p 0.375), while RVLS showed a significant improvement (-12.3% [-16.6 / -10.6] vs -16.9% [-20 / -11.7], p 0.007) (Figure). Conclusions These preliminary data, population on optimal medical therapy including ARNI confirm the role of SGLT2-i in left ventricular reverse remodeling. Of note, these medications seem to improve right ventricular function as well as the left one as demonstrated by the increase of RVLS, which seems to be more sensitive of conventional methods to assess right ventricular function. Larger studies are necessary to confirm the positive effects of SGLT2i on right ventricular function.

802 DIAGNOSTIC YIELD AND PREDICTIVE VALUE ON LEFT VENTRICULAR REVERSE REMODELING OF GENETIC TESTING IN DILATED CARDIOMYOPATHY

Abstract Background Genetic testing is one essential element in the diagnostic workup of patients with idiopathic dilated cardiomyopathy (DCM), and genotype-phenotype correlations are still poorly understood. We assessed the diagnostic yield of genetic testing in a selected DCM cohort including both familial and nonfamilial cases and evaluated phenotypic differences and the relationship of left ventricular reverse remodeling (LVRR) with the presence of pathogenic (P) or likely pathogenic (LP) variants of disease-associated DCM genes. Methods From 680 outpatients with heart with reduced ejection fraction followed at our Heart Failure Outpatient Clinic we selected subjects with a diagnosis of DCM before 65 years of age and without secondary causes of DCM including ischemic, valvular, hypertensive, or drug-induced heart disease or myocarditis. All patients underwent extensive clinical, laboratory, and imaging evaluation at the time of diagnosis and during regular follow-up visits and were offered genetic investigations with Next Generation Sequencing (NGS) of 42 disease-associated DCM genes. Results Of 680 DCM outpatients, 70 fulfilled the definition of idiopathic DCM and 66 gave consent to undergo genetic investigation (median age at diagnosis 57 years, 68% males). A total of 18 pathogenic/likely pathogenic (P/LP) variants were identified in 16 patients (diagnostic yield 24%), the most common (7, 39% of all variants) involving the TTN gene, followed by lamin A/C (n=3), cytoskeleton Z-disk (n=3), motor sarcomeric (n=2), desmosomal (n=1), and ion channel (n=1) gene variants. At the time of DCM diagnosis, patients with P/LP had a higher left ventricular (LV) ejection fraction (LVEF) compared with subjects (31±11% vs 28±8%, p=0.17). After a median follow-up of 53 (IQR 20-111) months, P/LP-positive patients had lower systolic and diastolic blood pressure and higher plasma natriuretic peptide levels than patients without P/LP variants. Patients without P/LP variants exhibited a larger extent of LVRR, as reflected by the increase in LVEF (+14% vs. +1%, p=0.0008) and decrease in LVEDDi (-3 vs. -1 mm/m2, p=0.03) compared with subjects carrying P/LP variants (Figure). Conclusions Our results confirm the high diagnostic yield of genetic testing in selected DCM patients and suggest that identification of P/LP variants in DCM portends poorer left ventricular reverse remodeling in response to guideline-directed medical therapy.

640 QRS INDEX TO PREDICT CARDIAC RESYNCHRONIZATION THERAPY RESPONSE: A TRICENTRIC STUDY

Abstract Background Several studies have evaluated the role of QRS duration (QRSd) or QRS narrowing as predictor of response to cardiac resynchronization therapy (CRT) in order to reduce non-responders. However, their results have been conflicting. In our study we analyzed retrospectively a cohort of patients from three centers to better correlate the association between the relative change in QRS narrowing index (QI) and clinical outcome and prognosis in patients who underwent CRT implantation. Methods We included 398 patients in whom a CRT device was implanted in accordance with current guidelines in our three centres. Baseline clinical variables, echocardiographic parameters and pharmacological therapies were included. QRS duration before and after CRT implantation and QI [(pre implant QRS duration - QRS duration during CRT)/pre implant QRS duration × 100] were measured. Results Respect to echocardiographic follow up at 6 months, a significant improvement in all parameters (EF, LVEDV, LVESV) was observed. In 68% of patients, LVESV decreased by 10% or more. QI was significantly related to reverse remodelling (r = + 0.22; 95% CI: 0.11 to 0.32, p = 0.001). The cut-off value of QI that predicted best LV reverse remodelling after 6 months of CRT was 12.25% (sensitivity 65,49%, specificity 75%, area under the curve 0.7, p = 0.001). Regarding clinical outcomes at 12 mounths, a statistically significant difference was found between patients with a QI ≤ 12.25%, and those with a QI &amp;gt; 12.25%, in terms of NYHA class worsening (p 0,04). Another statistically significant difference was found analyzing the relation between QI and the causes of deaths, the mean of the QI of patients who died from cardiovascular causes was lower than patients who died of other causes. (p 0,0179). Conclusions Therefore decrease in QRSd after CRT initiation was related to greater echocardiographic reverse remodelling and better outcome from death or cardiovascular hospitalization. Even if larger studies are needed, QI seems to be an easy-to- measure variable that could be used or evaluated to predict CRT response.

974 SACUBITRIL-VALSARTAN AMELIORATES MITOCHONDRIAL FUNCTION IN A MURINE MODEL OF ISOPROTERENOL-INDUCED LEFT VENTRICULAR DYSFUNCTION

Abstract Background Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, has proven to promote left ventricular (LV) reverse remodelling in patients with heart failure (HF) with reduced ejection fraction. However, its molecular and tissue effects have not been fully elucidated yet, due to the paucity of preclinical studies, mostly based on ischaemic models. Aim To evaluate the effects of sacubitril/valsartan on LV remodelling and cardiac mitochondrial function in a murine model of non-ischaemic LV dysfunction. Methods Adult male transgenic mice with cardiac-specific hyperaldosteronism (AS mice) received subcutaneous isoproterenol injection (300 mg/kg BID over two days), to induce LV systolic dysfunction. Mice were then randomized to a 2-week treatment with saline (0,2 mL BID) (ISO-AS n=15), valsartan (26 mg/kg in 0,2 mL of saline) (ISO+V n=12) or sacubitril/valsartan (57 mg/kg in 0,2 mL of saline) (ISO+S/V n=12). Echocardiography was performed at baseline, day 7, 15 and 21 of treatment. Mice were sacrificed at day 21, and histological and immunochemical assays were performed. A control group (Ctrl-AS n=8), not receiving isoproterenol nor pharmacological treatment, was obtained. Results Treatment with sacubitril/valsartan, but not with valsartan, induced a significant improvement of LV ejection fraction (p=0.009 vs ISO-AS) and fractional shortening (p= 0.032 vs ISO-AS) after 2-week treatment. In both ISO+V and ISO+S/V groups, a trend toward reduction of the extent of myocardial fibrosis was detected at histological analysis, confirmed by the lower cardiac collagen 1/3 expression ratio (p= 0.074). ISO+V and ISO+S/V groups showed a significant recovery of mitochondrial morphology and inner membrane function meant for oxidative phosphorylation. Additionally, both treatments reverted the alterations of the expression of genes involved in mitochondrial distribution, transport of organic/inorganic compounds, myocardial cell death, and response to the superoxide. Conclusion In a murine model of non-ischaemic HF, sacubitril/valsartan proved to have beneficial effects on LV remodelling and on cardiac energetics by improving mitochondrial activity.

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 pilot study of using 25 mg BD sacubitril/valsartan effect in reverse LV remodeling: A single-center experience

A pilot study of using 25 mg BD sacubitril/valsartan effect in reverse LV remodeling: A single-center experience

Cardiac contractility modulation in heart failure with reduced ejection fraction treatment

Heart failure with reduced left ventricular ejection fraction (LV EF) (HFrEF) is a significant issue of health care due to increasing indexes of morbidity and mortality. The emergence of a number of drugs and implantable devices for the treatment of HFrEF has allowed improvement of patients' well-being and prognosis. However, high mortality and recurrent decompensated heart failure remain a substantial issue and stimulate the search for new methods of CHF treatment. Cardiac contractility modulation (CCM) is a method of managing patients with HFrEF. Available data from randomized clinical trials (RCT) indicate the efficacy of CCM in improvement of patients' well-being and quality of life. The question remains open: what effect does CCM have on LV reverse remodeling? Experimental data and results of observational studies suggest a possibility of reverse remodeling by CCM; however, this has not been confirmed in RCT. Also, it remains unclear how CCM influences the frequency of hospitalizations for decompensated heart failure and the death rate of patients with HFrEF. Results of both RCTs and observational studies have shown a moderate improvement of quality of life associated with CCM. Furthermore, RCTs have not found any increase in LV EF due to the therapy, nor has a meta-analysis of RCTs revealed any improvement of the prognosis associated with CCM. Further RCTs are needed to evaluate the effect of CCM on reverse remodeling, survival rate, and to determine the place of CCM in the treatment of patients with CHF.

Reverse Remodeling and Non-Contrast T1 Hypointense Infarct Core in Patients With Reperfused Acute Myocardial Infarction.

Non-contrast T1 hypointense infarct cores (ICs) within infarcted myocardium detected using cardiac magnetic resonance imaging (CMR) T1 mapping may help assess the severity of left ventricular (LV) injury. However, because the relationship of ICs with chronic LV reverse remodeling (LVRR) is unknown, this study aimed to clarify it. We enrolled patients with reperfused AMI who underwent baseline CMR on day-7 post-primary percutaneous coronary intervention (n=109) and 12-month follow-up CMR (n=94). Correlations between ICs and chronic LVRR (end-systolic volume decrease ≥15% at 12-month follow-up from baseline CMR) were investigated. We detected 52 (47.7%) ICs on baseline CMR by non-contrast-T1 mapping. LVRR was found in 52.1% of patients with reperfused AMI at 12-month follow-up. Patients with ICs demonstrated higher peak creatine kinase levels, higher B-type natriuretic peptide levels at discharge, lower LV ejection fraction at discharge, and lower incidence of LVRR than those without ICs (26.5% vs. 73.3%, P<0.001) at follow-up. Multivariate logistic regression analysis showed that the presence of ICs was an independent and the strongest negative predictor for LVRR at 12-month follow-up (hazard ratio: 0.087, 95% confidence interval: 0.017-0.459, P=0.004). Peak creatine kinase levels, native T1 values at myocardial edema, and myocardial salvaged indices also correlated with ICs. ICs detected by non-contrast-T1 mapping with 3.0-T CMR were an independent negative predictor of LVRR in patients with reperfused AMI.

Electrocardiogram Belt guidance for left ventricular lead placement and biventricular pacing optimization

Patients with ischemic cardiomyopathy, non-left bundle branch block, or QRS duration <150 ms have a lower response rate to cardiac resynchronization therapy (CRT) than did other indicated patients. The ECG Belt system (EBS) is a novel surface mapping system designed to measure electrical dyssynchrony via the standard deviation of the activation times of the left ventricle. The objectives of this study were to evaluate the efficacy of the EBS in patients less likely to respond to CRT and to determine whether EBS use in lead placement guidance and device programming was superior to standard CRT care. This was a prospective randomized trial of patients with heart failure and EBS-guided CRT implantation and programming vs standard CRT care. The primary end point was relative change in left ventricular end-systolic volume from baseline to 6 months postimplantation. A total of 408 patients from centers in Europe and North America were randomized. Although both patients with EBS and control patients had a mean improvement in left ventricular end-systolic volume, there was no significant difference in relative change from baseline (P = .26). While patients with a higher baseline standard deviation of the activation times derived greater left ventricular reverse remodeling, improvement in electrical dyssynchrony did not correlate with the extent of reverse remodeling. The findings of the present study do not support EBS-guided therapy for CRT management of heart failure with reduced ejection fraction.

Prediction of Left Ventricular Reverse Remodeling and Outcomes by Circulating Collagen-Derived Peptides

BackgroundMyocardial fibrosis may increase vulnerability to poor prognosis in patients with heart failure (HF), even in those patients exhibiting left ventricular reverse remodeling (LVRR) after guideline-based therapies. ObjectivesThis study sought to characterize fibrosis at baseline in patients with HF with left ventricular ejection fraction (LVEF) <50% by determining serum collagen type I–derived peptides (procollagen type I C-terminal propeptide [PICP] and ratio of collagen type I C-terminal telopeptide to matrix metalloproteinase-1) and to evaluate their association with LVRR and prognosis. MethodsPeptides were determined in 1,034 patients with HF at baseline. One-year echocardiography was available in 665 patients. Associations of peptides with 1-year changes in echocardiographic variables were analyzed by multivariable linear mixed models. LVEF was considered improved if it increased by ≥15% or to ≥50% or if it increased by ≥10% to >40% in patients with LVEF ≤40%. Cardiovascular death and HF-related outcomes were analyzed in all patients randomized to derivation (n = 648) and validation (n = 386) cohorts. ResultsContinuous associations with echocardiographic changes were observed only for PICP. Compared with high-PICP (≥108.1 ng/mL) patients, low-PICP (<108.1 ng/mL) patients exhibited enhanced LVRR and a lower risk of HF-related outcomes (P ≤ 0.018), with women and nonischemic patients with HF showing a stronger LVEF increase (interaction P ≤ 0.010). LVEF increase was associated with a better prognosis, particularly in low-PICP patients (interaction P ≤ 0.029). Only patients with both low PICP and improved LVEF exhibited a better clinical evolution than patients with nonimproved LVEF (P < 0.001). ConclusionsPhenotyping with PICP, a peptide associated with myocardial fibrosis, may be useful to differentiate patients with HF who are more likely to experience clinical myocardial recovery from those with partial myocardial improvement.