Improvement In Cardiac Function Research Articles

Improvement in cardiac function but not structure in adults born preterm following a prescribed moderate to high intensity exercise intervention: a randomized clinical trial

Abstract Background People born preterm (<37 weeks’ gestation) have a potentially adverse cardiac phenotype that progresses with blood pressure elevation and may explain their increased risk of early heart failure and cardiovascular-related mortality. It remains unknown whether lifestyle or pharmacological interventions lead to beneficial left ventricle (LV) and right ventricle (RV) structural and/or functional changes in preterm-born adults. Purpose To determine whether preterm-born adults with elevated and stage 1 hypertension exhibit similar cardiac remodelling following a 16-week aerobic exercise intervention as their term-born peers with comparable blood pressures. Methods We conducted an open, parallel, two-arm superiority randomised controlled (1:1) trial in n=203 adults aged 18-35 years old with elevated or stage 1 hypertension. Participants were randomised to a 16-week aerobic exercise intervention targeting three, 60-minute supervised sessions per week at 60-80% peak heart rate (exercise intervention) or sign-posted to educational materials (controls). In a pre-specified cardiovascular magnetic resonance imaging (CMR) sub-study in n=100 individuals, CMR was performed before and after the 16-week intervention. Group differences in outcome variables after the intervention were examined using ANCOVA adjusting for baseline outcome variables, sex, and age. Interactions between birth category and intervention effect were investigated by including an interaction term in the intervention ANCOVA analyses. Results One hundred participants completed CMR scans at baseline and after the 16-week intervention, with n=47 in the exercise intervention group (n=26 term-born; n=21 preterm-born) and n=53 controls (n=32 term-born; n=21 preterm-born). Cardiac structural measures in preterm-born adults did not change following the intervention. However, term-born adults in the exercise intervention group decreased LV mass to end-diastolic volume ratio (adjusted mean difference: -0.03, 95% CI: -0.06,-0.01, interaction term p=0.027) and increased RV stroke volume (adjusted mean difference: 5.53mL/m2, 95% CI: 2.60,8.47, interaction term p=0.076) versus controls. Preterm-born adults in the exercise intervention group increased LV basal- and mid-ventricular circumferential strain versus controls (adjusted mean difference: -1.33%, 95% CI: -2.07,-0.60, interaction term p=0.057 and adjusted mean difference: -1.54%, 95% CI: -2.46,-0.63, interaction term p=0.046, respectively), which was not observed in term-born adults. Similarly, preterm-born adults improved RV longitudinal strain versus controls (adjusted mean difference: -0.51%, 95% CI: -1.49,0.46, interaction term p=0.053), which was also not observed in term-born adults. Conclusions Aerobic exercise training improves myocardial function but not cardiac structure in preterm-born adults. Modified exercise protocols or combination with pharmacological intervention may lead to additional cardiac remodelling benefits.

Treatment strategy for heart failure patients with guideline-directed medical therapy intolerance: a real-world prospective study

Abstract Background Guideline-directed medical therapy (GDMT) reduces the incidence of worsening events in patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, in actual clinical practice, a proportion of patients are unable to tolerate complete GDMT. Purpose This study aimed to assess the medication strategy for patients with HFrEF who are intolerant to GDMT. Methods A total of 110 patients admitted with acute HF were included in the study. The patients were non-randomly assigned to receive complete or incomplete GDMT after assessment by doctors before discharge from the hospital. All patients were followed up for 180 days. The primary composite endpoint was worsening HF-associated events, including death or rehospitalization due to HF, and the need for intravenous diuretic therapy. The secondary endpoints were the New York Heart Association functional class, blood pressure, and cardiac structure and function assessed by echocardiography. Results The main reasons for GDMT intolerance were renal insufficiency (41.8%) and hypotension (26.4%). GDMT-intolerant patients had lower eGFR (50.4 ml/min/1.73 m² vs. 70.9 ml/min/1.73 m²; p=0.002) compared with those who tolerated GDMT, and included more patients with chronic kidney disease (56.4% vs. 23.6%, p<0.001) and higher NT-proBNP levels (5340 pg/ml vs 8080 pg/ml, p=0.039) at baseline. While patient mortality was similar between the two groups, the rate of worsening HF events was lower in patients with GDMT (hazard ratio: 0.736; 95% confidence interval: 0.389−1.393) and vericiguat treatment (p<0.001). In terms of the secondary endpoint, patients who received GDMT showed greater improvements in cardiac structure and function although there was no statistical difference between the groups. In the prespecified subgroup analysis of the effects of vericiguat on the primary endpoint, the incidence of worsening HF events was reduced by vericiguat, regardless of whether the patient was comorbid with GDMT or not, or whether they had a previous history of HF (p-interaction= 0.519 and 0.227, respectively). Conclusions Patients with early in-hospital initiation of complete GDMT and continuous GDMT after discharge had better outcomes compared with patients who were intolerant to GDMT. Co-administration of vericiguat with or without GDMT may reduce the incidence of worsening HF events in HF patients within 180 days.Results of the primary endpoint

Exploring the long-term effects of dapagliflozin in patients with stable acute myocardial infarction and preserved ejection fraction through a propensity score matching study

Abstract Background and Aims The recent Emmy trial underscored notable improvements in cardiac structure and function among post-acute myocardial infarction (AMI) patients treated with Empagliflozin, compared to those receiving a placebo. However, limitations such as a small sample size and a short follow-up period hindered the assessment of potential differences in actual clinical events between the groups. Consequently, our study aimed to evaluate the long-term outcomes, survival rates, rates of major adverse cardiovascular events (MACE), and heart failure (HF) incidence in patients with preserved ejection fraction (EF) who experienced AMI and underwent successful percutaneous coronary intervention (PCI), comparing those who received early initiation of Dapagliflozin with those who did not. Methods Data from the Taipei Medical University Research Database in Taiwan identified 7,081 inpatients who met the criteria of AMI status post successful PCI, with a left ventricular ejection fraction (LVEF) greater than 50% and absence of clinical symptoms indicative of heart failure. Exclusion criteria included individuals with a pre-existing diagnosis of heart failure before the index AMI episode and those with an LVEF below 50%, resulting in the exclusion of 357 patients from our study. The study subjects were then divided into two groups: those treated with Dapagliflozin and those not treated with Dapagliflozin, with matching for age, diabetes mellitus, and chronic kidney disease in a 1:2 ratio. Results The cohort study included of 756 patients who met the criteria of this study, among whom 252 were Dapagliflozin users and 504 were not. Over a 7-year follow-up period, Kaplan-Meier survival analyses revealed a significant reduction in cardiovascular mortality and all-cause mortality among Dapagliflozin users compared to non-users (p < 0.01). However, no significant differences were observed in heart failure, recurrent AMI, or stroke during the follow-up. Multivariate Cox analysis indicated the use of Dapagliflozin (hazard ratio = 0.310, 95% confidence interval = 0.188-0.510, p < 0.001) and age of diagnosis (hazard ratio = 1.063, 95% confidence interval =1.045-1.081, p < 0.001) were both independent predictors of all cause death. Conclusions In patients with stabilized AMI, the use of Dapagliflozin was associated with a decreased risk of all-cause death, especially cardiovascular mortality. However, there were no significant differences observed in the rates of heart failure, recurrent AMI, or stroke over the seven-year follow-up period.Baseline characteristicsKaplan–Meier curves of all cause death

Fenofibrate modulates cardiac energy metabolism in moderate-severe aortic stenosis: a mechanistic double-blinded randomised controlled MR trial

Abstract Background Aortic stenosis (AS) is associated with impaired cardiac metabolism and high-energy phosphate production which can further exacerbate the progression to HF. Myocardial lipid accumulation and reduced production of high-energy phosphates have important implications for both systolic and diastolic heart function in AS. Peroxisome proliferator-activated receptor alpha (PPAR-alpha agonist, has the potential to optimise cardiac substrate metabolism, thereby, may be effective in improving cardiac dysfunction and functional capacity in AS. Methods In this prospective, randomized, double-blind, placebo-controlled study, patients with moderate-to-severe asymptomatic AS (n=72) were randomly assigned to Fenofibrate 200 mg daily or matching placebo for 6 months in 4:1 fashion. Of the total 72 participants, 59 received Fenofibrate and 13 received placebo. All subjects underwent cardiac magnetic resonance (CMR) and exercise testing at 0 and 6 months, with follow-up data available in 47 patients. The primary end point was change in myocardial triglyceride content (MTG) determined by proton magnetic resonance spectroscopy (1H-MRS). Secondary outcome measures included change in cardiac energetics (PCr/ATP) determined by phosphorus magnetic resonance spectroscopy (31P-MRS), left ventricular strain determined by myocardial tagging and exercise capacity i.e. peak VO2 assessment via cardiopulmonary exercise testing. Results Cardiac energetics (PCr/ATP) showed statistically significant improvement in the Fenofibrate group (0.14 ± 0.48; CI: - 0.03, 0.30; p=0.05) vs placebo group (0.11 ± 0.75; CI -0.42, 0.65; p=0.64). There was also significant reduction in MTG in the Fenofibrate group (mean change -0.40 ± 0.97; 95% CI -0.74, -0.06; p=0.02). MTG content also reduced in the placebo group (mean change -0.41 ± 0.26, 95% CI -1.10, 0.18, p 0.13), but the reduction was not statistically significant. Though no significant changes were seen in the systolic function parameters, there was a significant improvement in diastolic function in the fenofibrate group only (peak diastolic longitudinal strain rate 9.6, 95% CI: 1.13, 18.1; p = 0.02). Peak VO2 did not show any significant improvement in either group. Conclusions Fenofibrate works as a metabolic modulator upregulating fatty acid metabolism in pressure overload AS hearts. Such modulation is associated with an improvement in cardiac energetics and diastolic function in moderate-severe AS.Main results from baseline to 6 monthsBaseline demographic and CMR parameters

In-hospital initiation of Vericiguat and short-term cardiovascular function improvement in heart failure patients with worsened renal function

Abstract Background and Aims Vericiguat, a novel soluble guanylate cyclase (sGC) stimulator, is approved for treating heart failure (HF) with reduced ejection fraction (HFrEF). This study aims to assess the short-term improvement in cardio-function resulting from in-hospital initiation of Vericiguat among patients with chronic kidney dysfunction (CKD), utilizing real-world data from a single-center experience in western China. Method Data were obtained from the Biobank of our hospital, spanning from January 2023 to December 2023. A total of 213 HF patients with Vericiguat initiation were screened for eligibility. Echocardiography was employed to evaluate cardio-function after 1- and 3-month short-term follow-up in each patient. Statistical analyses were conducted using one-way ANOVA (followed by Geisser-Greenhouse correction and Tukey’s multiple comparison) to assess significance between different timepoints. Results Among the 213 patients randomized in this study, baseline characteristics were compared based on estimated glomerular filtration rate (eGFR) ≤ 30 (worsened renal function group, WRF, n = 20) and >30 mL/min/1.73 m2 (n = 193). No significant differences were observed in age, gender, and other biochemical parameters expect hemoglobin and creatine between the two groups (Table 1). Analysis of cardiac function after 1- and 3-month follow-up revealed a promising increase in left ventricular ejection fraction (EF) (37.2% vs. 43.9%, Mean diff -6.7, 95% CI -12.78 to -0.62, p = 0.03), fractional shortening (FS) (20.9% vs. 25.3%, Mean diff -4.42, 95% CI -8.57 to -0.27, p = 0.04), and a significant decrease in left ventricular end-diastolic dimension (LVEDD) (65.0mm vs. 60.6mm, Mean diff 4.35, 95% CI 0.33 to 8.38, p = 0.03) after 3-month follow-up compared to Vericiguat initiation in WRF patients. However, no significant changes were observed between the beginning and 1-month follow-up in echocardiographic measurements (Figure 1). Conclusion In this real-world single-center study, Vericiguat demonstrated effectiveness in short-term improvement of cardiac function among HF patients with worsened renal function. The long-term efficacy in reducing major cardiovascular events in this subgroup, based on real-world experience, warrants further exploration.

Growth differentiation factor 11 alleviates oxidative stress-induced senescence of endothelial progenitor cells via activating autophagy

BackgroundStem cell transplantation has been regarded as a promising therapeutic strategy for myocardial regeneration after myocardial infarction (MI). However, the survival and differentiation of the transplanted stem cells in the hostile ischaemic and inflammatory microenvironment are poor. Recent studies have focused on enhancing the survival and differentiation of the stem cells, while strategies to suppress the senescence of the transplanted stem cells is unknown. Therefore, we investigated the effect of growth differentiation factor 11 (GDF11) on attenuating oxidative stress-induced senescence in the engrafted endothelial progenitor cells (EPCs).MethodsRat models of oxidative stress were established by hydrogen peroxide conditioning. Oxidative stress-induced senescence was assessed through senescence-associated β-galactosidase expression and lipofuscin accumulation. The effects of GDF11 treatment on senescence and autophagy of EPCs were evaluated 345, while improvement of myocardial regeneration, neovascularization and cardiac function were examined following transplantation of the self-assembling peptide (SAP) loaded EPCs and GDF11 in the rat MI models.ResultsFollowing hydrogen peroxide conditioning, the level of ROS in EPCs decreased significantly upon treatment with GDF11. This resulted in reduction in the senescent cells and lipofuscin particles, as well as the damaged mitochondria and rough endoplasmic reticula. Concurrently, there was a significant increase in LC3-II expression, LC3-positive puncta and the presence of autophagic ultrastructures were increased significantly. The formulated SAP effectively adhered to EPCs and sustained the release of GDF11. Transplantation of SAP-loaded EPCs and GDF11 into the ischaemic abdominal pouch or myocardium resulted in a decreased number of the senescent EPCs. At four weeks after transplantation into the myocardium, neovascularization and myocardial regeneration were enhanced, reverse myocardial remodeling was attenuated, and cardiac function was improved effectively.ConclusionsThis study provides novel evidence suggesting that oxidative stress could induce senescence of the transplanted EPCs in the ischemic myocardium. GDF11 demonstrates the ability to mitigate oxidative stress-induced senescence in the transplanted EPCs within the myocardium by activating autophagy.

His Bundle Pacing and Left Bundle Branch Pacing in Patients with Heart Failure.

His bundle pacing (HBP) and left bundle branch pacing (LBBP) are emerging therapies for patients with heart failure and conduction disorders, offering potential advantages over traditional pacing methods. These approaches aim to restore physiological conduction and improve cardiac function more effectively. This study aims to evaluate the efficacy and safety of HBP and LBBP in patients with heart failure and conduction disturbances, comparing these techniques to conventional pacing. A comprehensive review of recent studies and clinical trials was conducted, focusing on the performance of HBP and LBBP in improving cardiac function, reducing QRS duration, and enhancing overall patient outcomes. The analysis includes data on clinical efficacy, procedural safety, and long-term benefits associated with these pacing modalities. Both HBP and LBBP have demonstrated significant improvements in cardiac function and clinical outcomes compared to conventional pacing. HBP effectively restores physiological conduction with improved synchronization and a reduction in QRS duration. LBBP has shown enhanced left ventricular activation, leading to better overall cardiac performance. Both techniques have been associated with a lower incidence of complications and a higher success rate in achieving optimal pacing thresholds. HBP and LBBP offer promising alternatives to traditional pacing for patients with heart failure and conduction disorders. These advanced pacing strategies provide superior clinical outcomes and improved cardiac function with reduced risk of complications. Further research and clinical trials are needed to fully establish the long-term benefits and safety profiles of these techniques in diverse patient populations.

A retrospective study on the relationship between plasma β-hydroxybutyric acid levels and short-term prognosis of cardiac function in patients with acute myocardial infarction combined with heart failure

Abstract Background Ketone body metabolism can improve cardiomyocytes metabolism and reduce myocardial oxygen consumption; however, its role in the short-term prognosis of patients with acute myocardial infarction combined with heart failure has not been clearly elucidated. The aim of this study was to investigate the effect of β-hydroxybutyric acid, the main component of ketone bodies, on the short-term prognosis of patients with acute myocardial infarction combined with heart failure. Methods This was a retrospective observational study that enrolled patients admitted to the Qilu Hospital of Shandong University for acute myocardial infarction combined with heart failure between January 1, 2019, and December 31, 2022. According to whether β-hydroxybutyric acid was elevated or not, subjects were divided into a β-hydroxybutyric acid elevated and nonelevated groups, to observe the difference in cardiac function improvement between the two groups. Results This study included a total of 260 patients, of which 170 exhibited elevated levels of β-hydroxybutyric acid. Compared to the patients in the nonelevated group, patients in the elevated β-hydroxybutyric acid group had higher plasma levels of creatine kinase myocardial band and greater Gensini scores. Multivariate logistic regression analysis indicated that an increase in β-hydroxybutyric acid levels (odds ratio: 2.517; 95% confidence intervals: 1.394–4.597; P = 0.002) is an independent protective factor affecting the prognosis of cardiac function in patients with acute myocardial infarction combined with heart failure. Conclusion In patients with acute myocardial infarction combined with heart failure, plasma β-hydroxybutyric acid serves as an independent protective factor for short-term improvement in cardiac function.

Causes and Diagnostic Significance of Coughing in Dogs with Endocardiosis

Introduction. Endocardiosis is the most widespread acquired cardiac disease in small dog breeds, characterised by the valvular degeneration leading to mitral insufficiency. Progression of mitral regurgitation leads to cardiac remodeling, increased left ventricular filling pressures, pulmonary hypertension and, eventually, myocardial dysfunction. Decreased exercise tolerance, dyspnea, anorexia, and coughing are the most often reported signs in dogs with endocardiosis. Coughing is often reported as the primary clinical sign of congestive heart failure in dogs with endocardiosis. The concomitant respiratory tract disease and compression of the left mainstem bronchus by the giant left atrium have also been suggested as the potential causes of coughing in these patients. However, the absence of relief from cough in dogs with endocardiosis when treated with calcium sensitizers and the registered improvement in systolic cardiac function makes doubtful the cardiogenic nature of coughing in endocardiosis. In other words, the clinical and diagnostic significance of coughing in dogs with endocardiosis has not been sufficiently studied. The aim of the present research is to determine the frequency of cough incidence in dogs with endocardiosis and to establish the pathognomonic nature of this symptom in endocardiosis, its clinical significance.Materials and Methods. The medical records of 49 dogs that have attended to the veterinary clinics of the “Vita” network (Rostov region) for cardiological examination in the period from September 1, 2021 to July 31, 2024 were analysed. The research was carried out using the following equipment: premium ultrasound scanner with improved image quality on the ZST+ Mindray Vetus 9 platform, Maxivet 400 veterinary X-ray digital DR system, and Poli-Spectrum–8/V computerassisted electrocardiograph.Results. The research allowed us to find out the following: although the cardiomegaly and the increase in the size of the left ventricle in endocardiosis can aggravate and intensify the clinical manifestation of coughing in dogs with degenerative diseases of the upper respiratory tract, they are not the necessary condition for the occurrence of coughing. Coughing in dogs with endocardiosis should be considered as a clinical sign of the concomitant inflammatory or degenerative disease of the upper respiratory tract, which should be taken into account in therapy and in the attempt to improve the quality of life of these animals.Discussion and Conclusion. We have found that only 57% of the dogs with clinically evident endocardiosis suffer from coughing, whereas it does not have the uniform nature. In dogs with cardiogenic pulmonary edema, a cough is not loud, is usually acute and is associated with the flow of fluid into the medium and large-sized bronchi. The chronic loud, hoarse cough, intensifying in the morning, is typical for dogs with endocardiosis and chronic bronchitis: these animals at the same time have the non-specific inflammatory lesion of the bronchial tree and lesion of the mitral valves. Most severe coughing, with the characteristic loud sound, is observed in dogs suffering from the elements of the upper respiratory tract collapse and cardiomegaly due to endocardiosis.

Bariatric surgeries and cardiac structure and function: Systematic review and network meta-analysis.

Obesity, a global health problem, is causally implicated in the development of cardiovascular disease. Bariatric surgeries are effective treatment options for obesity; however, the effectiveness of different bariatric surgeries on cardiac structure and function is not fully understood. We undertook a systematic review and network meta-analysis to comprehensively assess this effectiveness. PubMed, Web of Science, and EMBASE were searched from their inception until November 11, 2023. Studies that compared bariatric surgeries vis-à-vis non-surgical treatment, placebo, and other bariatric surgeries, as well as reported changes in left ventricular mass or its index (LVM or LVMI) or left ventricular ejection fraction (LVEF), were summarized. Total 19 studies (17 cohort studies and 2 randomized controlled trials) and 2012 adults were meta-analyzed. Patients receiving gastric bypass had appreciably lowered LVM (weighted mean difference [WMD]: -43.86 g, 95% confidence interval [CI] -61.09 to -26.63, p < 0.01) and LVMI (standardized mean difference: -0.67, 95% CI -1.03 to -0.32, p < 0.01) compared with other bariatric surgeries. No significant improvement in LVEF was noted across all surgeries. The drop in body mass index was most pronounced for biliopancreatic diversion with duodenal switch (WMD -16.33 kg/m2, 95% CI -21.60 to -11.05, p < 0.01). Our findings of this network meta-analysis indicated that gastric bypass proved best for the improvement in cardiac structure, and there was no obvious improvement in cardiac function for all bariatric surgeries. Further studies are required to better understand the differing effectiveness of bariatric surgeries on cardiac structure and function and the underlying molecular mechanisms.

Aptamer BT200 is protective against myocardial ischemia-reperfusion injury in mice

BackgroundMyocardial ischemia-reperfusion (MI/R) injury tends to affect cardiac function and leads to poor patient prognosis, and there is still no effectively targeted drug to develop anti–von Willebrand factor (VWF) aptamer in acute coronary heart disease. However, the newly anti-VWF aptamer BT200 is applied not only for stroke and hemophilia but also for antithrombolism function in clinical development. The role of BT200 in acute myocardial injury during MI/R is still unknown. ObjectivesTo investigate the cardioprotective effect of aptamer BT200 in a mouse model of MI/R. MethodsC57BL/6 mice were subjected to 30-minute ischemia and 24-hour reperfusion to establish MI/R model. Mice were treated with intravenous injection of cy3-labeled BT200 and were observed by an in vivo imaging system at different time points. Then, mice were sampled and evaluated by echocardiography, Evans triphenyltetrazolium chloride staining, histopathologic, western blotting, and real-time quantitative polymerase chain reaction assays to detect cardiac injury and inflammation response after 24-hour reperfusion. ResultsBT200 aptamer can enter and infiltrate into the ischemic myocardium after 24-hour reperfusion. BT200 was shown to inhibit VWF A1 activity and prolong bleeding time in MI/R mice. Moreover, BT200-treated mice had a significant reduction in infarct size and an improvement in cardiac function post-MI/R. BT200 treatment can also alleviate MI/R-induced microvascular obstruction, inflammation response, and cardiomyocyte apoptosis. ConclusionPharmacologic targeting of VWF with BT200 alleviates acute MI/R injury in a murine model and may be a novel therapy strategy for acute myocardial infarction.

A Novel Human Amniotic Membrane Suspension Improves the Therapeutic Effect of Mesenchymal Stem Cells on Myocardial Infarction in Rats

Mesenchymal stem cell (MSC) therapy aids cardiac repair and regeneration, but the low rate of MSC survival and engulfment in the infarcted heart remains a major obstacle for routine clinical application. Here, an injectable suspension of human acellular amniotic membrane (HAAM) that may serve as synergistic cell delivery vehicle for the treatment of myocardial infarction (MI) by improving MSC homing and survival is developed. The results demonstrate that compared with MSC transplantation alone, HAAM‐loaded MSCs have higher survival and engraftment rates in infarcted tissue, alleviated hypoxia‐induced myocardial damage, achieved higher improvements in cardiac function, promoted angiogenesis, and reduced myocardial fibrosis. In addition, HAAM‐loaded MSCs increase N‐cadherin levels and thereby enhance the efficacy of MSCs in treating MI. This study provides a new approach for MSC‐based cardiac repair and regeneration.

Cardiac and kidney outcomes after sacubitril-valsartan therapy: recovery of cardiac function relative to kidney function decline.

Sacubitril-valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction (HFrEF). However, its long-term protective effects on cardiac function with concurrent acute kidney injury (AKI) remain unclear. This study investigated the recovery of cardiac function relative to kidney function decline. A total of 512 patients with HFrEF who started sacubitril-valsartan or valsartan treatment were enrolled in cohort 1. Additionally, patients who experienced AKI and underwent follow-up transthoracic echocardiography were enrolled in cohort 2. In cohort 1, short- and long-term kidney outcomes were analyzed. For cohort 2, changes in cardiac function in relation to changes in kidney function after drug initiation were analyzed. The mean age of the patients was 68.3 ± 15.1 years, and 57.4% of the patients were male. AKI occurred in 15.9% of the sacubitril-valsartan group and 12.5% of the valsartan group. After AKI, 78.4% of patients in the sacubitril-valsartan group and 71.4% of those in the valsartan group underwent recovery. Furthermore, cardiovascular outcomes in patients who developed AKI after drug initiation were analyzed in cohort 2. The sacubitril-valsartan group showed a greater improvement in cardiac function compared with the valsartan group (12.4% ± 15.4% vs. 1.4% ± 5.7%, p = 0.046). The ratio of deltas of cardiac and kidney function in the sacubitril-valsartan and valsartan groups were -1.76 ± 2.58 and -0.20 ± 0.58, respectively (p = 0.03). Patients with HFrEF treated with sacubitril-valsartan exhibited significant improvements in cardiovascular outcomes despite AKI.

A comparative study on the effect of coronary angioplasty on left ventricular function in post myocardial infarction among patients with and without type-2 diabetes mellitus

Background and objectives. Coronary angioplasty is a common intervention for improving cardiac function postmyocardial infarction. However, the impact of this procedure in patients with type-2 diabetes mellitus (T2DM) compared to those without diabetes remains less understood. Material and methods. This study included 50 patients who underwent coronary angioplasty post-myocardial infarction. Patients were divided into two groups based on the presence (Group A) or absence (Group B) of T2DM, with 6 patients in each group. We assessed left ventricular function using echocardiography, focusing on ejection fraction and wall motion score, at baseline, and at 1, 3, and 6 months post-angioplasty. Additional data on clinical outcomes, functional status, cardiac biomarkers, medication use, comorbid condition management, and hemodynamic measurements were also collected. Results. Both groups showed improvement in left ventricular function post-angioplasty, with no significant difference in ejection fraction and wall motion score between the two groups at each follow-up. Clinical outcomes, functional status, and biomarker levels were comparable between groups. Medication compliance was high in both groups. The control of comorbid conditions and hemodynamic stability post-angioplasty were similarly maintained in both diabetic and nondiabetic patients. Conclusion. Coronary angioplasty positively impacts left ventricular function in post-myocardial infarction patients, irrespective of the presence of T2DM. Both diabetic and non-diabetic patients demonstrated similar improvements in cardiac function and overall clinical outcomes, suggesting that angioplasty is an effective intervention for post-myocardial infarction patients regardless of their diabetes status. Further studies with larger sample sizes are recommended to validate these findings.

Mechanistic insights into Suanzaoren Decoction's improvement of cardiac contractile function in anxiety-induced cardiac insufficiency

Ethnopharmacological relevanceAccording to traditional Chinese medicine, Anxiety-induced cardiac blood insufficiency leads to palpitations and restlessness. Suanzaoren Decoction (SD) is effective in replenishing blood and promoting blood circulation. Clinical practice has shown that it has a better therapeutic effect on cardiac insufficiency. However, its mechanism of action is still unclear. Aim of the studyThe study aims to determine the mechanism by which SD treats chronic restraint stress (CRS)-induced anxiety-induced cardiac insufficiency (ACI). Materials and methodsSD was orally administered to mice with CRS-induced ACI. Firstly, we constructed an anxiety model in mice by CRS. Subsequently, SD was investigated to assess cardiac function and pathological changes through echocardiography, H&E staining, and Masson staining. Thirdly, the function of sympathetic and parasympathetic nerves was evaluated using enzyme-linked immunosorbent assay (ELISA) and enzyme activity assays. Network pharmacology and molecular docking were employed to predict potential targets for SD treatment of cardiac insufficiency. CaMKII expression was scrutinized utilizing publicly accessible databases. CaMKII was identified as a target through immunohistochemistry and Western Blot analysis in mouse hearts. Finally, the therapeutic mechanism of SD was confirmed in injured cardiomyocytes via Western Blot and quantitative PCR. ResultsSD exerted anxiolytic effects by increasing the frequency of entries into and the duration spent in open arms while reducing the time spent in the light chamber and increasing the number of transitions between light and dark chambers. Additionally, it mitigated cardiac insufficiency, as evidenced by the enhancement of left ventricular ejection fraction (LVEF) and attenuation of cardiomyocyte damage and inflammatory infiltration.However, SD did not alleviate the elevated norepinephrine (NE) and decreased Acetylcholine (Ach) in anxiety states. To investigate the mechanism of action of SD, we constructed a Drug-Component-Target-Disease network, identifying 13 potential active compounds. Additionally, leveraging bioinformatics analysis and molecular docking targeting heart diseases characterized by clinical left ventricular ejection fraction (LVEF), we focused on the CaMKII target. The ability of SD to modulate CaMKII expression and phosphorylation in the mouse heart was investigated using immunohistochemistry and Western blotting. SD was found to alleviate NE-injured cardiomyocytes by modulating the Ca2+/CaMKII/MEF2 and GATA4 pathways. ConclusionSD is a potential formula for the treatment of chronic restraint stress (CRS)-induced ACI that ameliorates cardiomyocyte injury and improves cardiac function. Its efficacy is associated with the inhibition of the Ca2+/CaMKII/MEF2 and GATA4 signaling pathways.

Permanent left bundle branch area pacing improves mitral regurgitation and cardiac function in patients with right bundle branch block

BackgroundPermanent left bundle branch area pacing (LBBAP) has been established as an effective means to correct left bundle branch block. Right bundle branch block (RBBB), emerge as a distinct form of cardiac conduction abnormality, can be seen in the context of LBBAP procedure. However, the correction potential of LBBAP in patients with RBBB remains largely unexplored.ObjectiveThe objective of this study was to evaluate the efficacy and safety of permanent LBBAP in patients with RBBB.MethodsNinety-two consecutive patients who underwent successful permanent LBBAP were recruited from May. 2019 to Dec. 2022 in Fuwai Central China Cardiovascular Hospital. Among them, 20 patients with RBBB were included in our analysis. These patients were followed up at 1, 3, 6 and 12 months post-LBBAP. The QRS duration (QRSd) on the V1 lead of the 12-lead elctrocardiogram was measured and compared before and after the LBBAP procedure. Additionally, mitral regurgitation, tricuspid regurgitation and cardiac function were assessed using transthoracic echocardiography, specifically focusing on left ventricular ejection fraction (LVEF) and mitral regurgitation severity. The acute pitfills and delayed complications associated with the LBBAP procedure were recorded to evaluate its safety. SPSS 23.0 was used to perform statistical analysis with Student’s t test or one way ANOVA or nonparametric tests (paired Wilcoxon test). A p value less than 0.05 was defined as significant.ResultsThe demographic breakdown of the RBBB cohort revealed a mean age of 66.35 ± 11.55 years, 60% being male. Comorbidities were prevalent, including severe atrioventricular block (AVB) in 75%, sick sinus syndrome (SSS) in 20%, heart failure in 25%, atrial fibrillation in 30%, coronary heart diseases in 45%, hypertension in 35%, and diabetes mellitus in 15%. Regarding the LBBAP procedure, the average operation time was 106.53 ± 2.72 min, with 45% of patients (9 individuals) requiring temporary cardiac pacing during the surgery. Notably, the LBBAP procedure significantly narrow the QRS duration in RBBB patients, from 132.60 ± 31.49ms to 119.55 ± 18.58 ms (P = 0.046). Additionally, at the 12-month follow-up, we observed a marked improvement in LVEF, which increased significantly from 55.15 ± 10.84% to 58.5 ± 10.55% (P = 0.018). Furthermore, mitral regurgitation severity improved, with a median reduction from 4.46 (0.9, 7.3) to 2.29 (0, 3.49) cm2 (P = 0.033). Importantly, no cases of ventricular septum perforation or pericardial effusion were reported during the LBBAP procedure or during the follow-up period.ConclusionLBBAP provides an immediate reduction in QRS duration for patients suffering from RBBB, accompanied by improvements in mitral regurgitation and cardiac function as evident in the 12-month follow-up period.

Letrozole-induced reversible acute heart failure.

Letrozole is an aromatase inhibitor (AI), which suppresses plasma estrogen levels by inhibiting the aromatase enzyme, that causes the conversion of androgens to estrogen in peripheral tissues. There is very few information in the literature regarding the development of acute heart failure after AI use. We would like to report a case of a patient who was started letrozole for hormonal treatment and developed acute heart failure due to this. Fifty-seven-year-old woman with hormone positive breast cancer was operated after neoadjuvant chemotherapy and received radiotherapy. Letrozole treatment was initiated after radiotherapy and the patient presented to the emergency department after two weeks with cough and dyspnea. Ejection fraction decreased to 20% and acute heart failure developed. Letrozole treatment was stopped. Afterwards, improvement in the patient's cardiac functions was observed. Letrozole-induced heart failure was thought to be reversible. Letrozole is one of the most commonly used HT in the treatment of hormone positive breast cancer. It may rarely cause cardiac side effects. It is very important to make patients aware of these issues and to be consulted by cardiology in case of possible cardiac symptoms.

Inhibition of 5-alpha reductase attenuates cardiac oxidative damage in obese and aging male rats via the enhancement of antioxidants and the p53 protein suppression

In aging and metabolic syndrome oxidative stress is a causative factor in the cardiovascular pathology. Upregulation of 5-⍺ reductase is associated with cardiac hypertrophy but how inhibition of 5-⍺ reductase affects cardiometabolic function during oxidative damage under those conditions is unclear. Our hypothesis was that Finasteride (Fin), a 5-⍺ reductase inhibitor, promotes an antioxidant response, leading to an improvement in cardiac function in obese and aging rats. Male rats were divided into 3 groups including normal diet (ND) fed rats, ND-fed rats treated with d-galactose (D-gal) to induce aging, and high-fat diet (HFD) fed rats to induce obesity. Rats received their assigned diet or D-gal for 18 weeks. At week 13, rats in each group were divided into 2 subgroups and received either a vehicle or Fin (5 mg/kg/day, oral gavage). Cardiometabolic and molecular parameters were subsequently investigated. Both D-gal and HFD successfully induced cardiometabolic dysfunction, oxidative stress, mitochondrial dysfunction, and DNA fragmentation. Fin treatment did not affect metabolic disturbances; however, it reduced cardiac sympathovagal imbalance, cardiac dysfunction through the inhibition of oxidative stress and promoted antioxidants, resulting in reduced p53 protein levels and DNA fragmentation. Surprisingly, Fin induced insulin resistance in ND-fed rats. Fin effectively improved cardiac function in both models by enhancing antioxidant levels, suppressing oxidative stress and DNA fragmentation. However, Fin treatment did not confer any beneficial effects on metabolic status. Fin administration effectively improved cardiac sympathovagal balance and cardiac function in rats with oxidative damage induced by either D-gal or HFD.

Metformin modulates microbiota and improves blood pressure and cardiac remodeling in a rat model of hypertension.

Metformin has been attributed to cardiovascular protection even in the absence of diabetes. Recent observations suggest that metformin influences the gut microbiome. We aimed to investigate the influence of metformin on the gut microbiota and hypertensive target organ damage in hypertensive rats. Male double transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR), a model of angiotensin II-dependent hypertension, were treated with metformin (300 mg/kg/day) or vehicle from 4 to 7 weeks of age. We assessed gut microbiome composition and function using shotgun metagenomic sequencing and measured blood pressure via radiotelemetry. Cardiac and renal organ damage and inflammation were evaluated by echocardiography, histology, and flow cytometry. Metformin treatment increased the production of short-chain fatty acids (SCFA) acetate and propionate in feces without altering microbial composition and diversity. It significantly reduced systolic and diastolic blood pressure and improved cardiac function, as measured by end-diastolic volume, E/A, and stroke volume despite increased cardiac hypertrophy. Metformin reduced cardiac inflammation by lowering macrophage infiltration and shifting macrophage subpopulations towards a less inflammatory phenotype. The observed improvements in blood pressure, cardiac function, and inflammation correlated with fecal SCFA levels in dTGR. Invitro, acetate and propionate altered M1-like gene expression in macrophages, reinforcing anti-inflammatory effects. Metformin did not affect hypertensive renal damage or microvascular structure. Metformin modulated the gut microbiome, increased SCFA production, and ameliorated blood pressure and cardiac remodeling in dTGR. Our findings confirm the protective effects of metformin in the absence of diabetes, highlighting SCFA as a potential mediators.

GPER Stimulation Attenuates Cardiac Dysfunction in a Rat Model of Preeclampsia.

Preeclampsia poses a substantial clinical challenge, characterized by maternal hypertension, cardiac dysfunction, and persistent cardiovascular risks for both the mother and offspring. Despite the known roles of the estrogen receptor (GPER [G protein-coupled estrogen receptor]) in placental development, its impact on cardiovascular aspects within a preeclampsia animal model remains unexplored. We propose that G-1, a GPER agonist, could have the potential to regulate not only hypertension but also cardiac dysfunction in rats with preeclampsia. To explore the influence of G-1 on preeclampsia, we used the reduced uterine perfusion pressure (RUPP) model. RUPP rats were administered either G-1 (100 µg/kg per day) or hydralazine (25 mg/kg per day). We conducted echocardiography to probe the intricate cardiac effects of G-1. The RUPP rat model revealed signs of hypertension and cardiac dysfunction and alterations in gene and protein expression within placental and heart tissues. G-1 treatment reduced blood pressure and reversed cardiac dysfunction in rats with preeclampsia. In contrast, administration of the vasodilator hydralazine reduced blood pressure without an improvement in cardiac function. In addition, while G-1 treatment restored the levels of sFLT-1 (soluble fms-like tyrosine kinase-1) in RUPP rats, hydralazine did not normalize this antiangiogenic factor. The therapeutic intervention of G-1 significantly mitigated the cardiovascular dysfunction observed in the RUPP rat model of preeclampsia. This discovery underscores the broader significance of understanding GPER's role in the context of preeclampsia-related cardiovascular complications.