Improvement In Cardiac Function Research Articles

#1677 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 the First Affiliated Hospital of Xi'an Jiaotong University, 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) (65.0 mm vs. 60.6 mm, 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 (Fig. 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.

#2770 Evaluation of the effect of IV iron therapy on eGFR and Pro-BNP in patients with chronic kidney disease and heart failure with preserved EF

Abstract Background and Aims Iron replacement in treating heart failure (HF) is an issue whose importance has been better understood in recent years. Although controversies exist, randomized controlled studies have shown that IV iron treatment reduces mortality and improves symptomatology in heart failure with low EF (HFrEF). IV iron has not dramatically affected survival in heart failure with preserved EF (HFpEF). However, there is data that it might reduce symptoms and hospitalizations. For patients with chronic kidney disease (CKD) and HF, around 60% of them have HFpEF. Major heart failure and iron studies have often been performed on patients with low EF. Furthermore, in some of these studies, GFR values were not reported, and in the others, GFR was often > 60 ml/minute. We planned this study to evaluate the effects of IV iron therapy on eGFR and Pro-BNP levels in non-dialysis CKD patients with HFpEF. Method This study was conducted between January 2022 and December 2023. Patients with iron deficiency anemia, stage 2-5ND chronic kidney disease, and those with Pro-BNP values of 1000 and above were selected. Two independent cardiologists evaluated them, and the diagnosis of heart failure was confirmed. Patients were given one dose of 500 or 1000 mg of FCM. Control values were obtained at the 1-month follow-up. Hospitalized or transfused patients, cases with primary hematological disease, and cases with conditions affecting ferritin levels were excluded. Patients whose RAAS blockade, SGLT-2 inhibitor, and diuretic doses were changed, were excluded from the analysis. No patients received ESA or HIF stabilizers. Demographic and clinical data of the patients were recorded. The patients' creatinine, eGFR, hemoglobin, ferritin, and pro-BNP levels were evaluated before and after iron treatment Results Seventy-four patients were recruited. Forty-seven patients were women. The average age was 68 ± 11 years. Forty-eight of the patients had diabetes (64.9%) and 47 (63.5%) had coronary artery disease. The etiology of HFpEF was diastolic heart failure in 45 patients (60%). Other patients had valve disease, HFmEF, HFimpEF, isolated right-sided HF, and mixed types of HFpEF. After IV iron treatment, an increase of 3 ± 1 ml/min in GFR and 1.1 ± 0.1 g/dL in hemoglobin was detected. ProBNP levels decreased by 46%. All findings were statistically significant. The findings are summarized in Table 1. Conclusion The decrease in ProBNP levels was similar to the HFrEF literature. No positive or negative effects of iron on GFR were observed in the REVOKE and FIND-CKD studies, which compared oral and IV iron in CKD patients. The small but significant increase in GFR in our study could be attributed to the improvement of cardiac function. However, the small number of patients and the short follow-up period make it difficult to reach a definitive conclusion on this issue. We have shown that IV iron treatment significantly reduces Pro-BNP levels in CKD patients with HFpEF. IV iron has no adverse effects on renal function in the short term, and there is little signal of potential positive effects. Longer-term studies, preferably randomized with oral iron, with appropriate sample size, are needed to evaluate how IV iron affects end-points such as HF symptom score, hospitalization, eGFR slope, need for renal replacement, and mortality in this patient group. Strengths Well-selected patient group, a high Pro-BNP cut-off point, re-evaluation of each patient by the cardiologists Limitations Relatively small cohort, short follow-up period

Gold nanoparticles-conjugation of irisin enhances therapeutic effect by improving cardiac function and attenuating inflammation in sepsis

Introduction: Irisin is considered to be a promising therapeutic approach for cardiac depression and inflammatory disorders. The short half-life of irisin impeded its use and drug effcacy in the treatment. Objective: This study aimed to examine if pegylated gold nanoparticles-conjugated to irisin would improve therapeutic effects in cecal ligation and puncture (CLP)-induced sepsis in mice. Method: Recombinant irisin were conjugated to a pegylated gold nanoparticle, which was given to mice exposed to CLP. The cecal ligation procedure and sham on mice were operated and assigned to one of following five groups: I) CLP group: The mouse models underwent the CLP surgical procedure and received only vehicle saline treatment (n= 5); II) CLP + soluble Irisin: The mouse underwent the CLP and received an i.m (TA) injection of 1 ug of soluble irisin into each leg (n= 5); III) CLP + Gold nanoparticle-conjugated to Irisin: The mouse models underwent the CLP and received an i.m (TA) injection of 1 μg of Gold nanoparticle-irisin via intramuscular injection (TA) into each leg w (n= 5); IV) CLP + Gold nanoparticles- conjugated to IgG: The mouse underwent the CLP and received an i.m (TA) injection of gold nanoparticles conjugated to IgG (n=5). V) Sham: The mouse underwent the surgical operation without conducting the CLP (n=10). The post-operated animals were observed for one week, and survival rates were estimated. Echocardiography was performed to measure cardiac function at 12 hours following CLP. TUNEL was employed to detect apoptosis in both cardiac and skeletal muscles; histology was conducted to assess tissue injury in muscles. Enzyme linked immunosorbent assay (ELISA) was conducted to examine release of interleukin 6 (IL6) and the tumor necrosis factor (TNF) alpha. Results: Compared to the CLP control, soluble irisin treatment improved cardiac function recovery, as indicated by the fractional shortening (FS) and ejection fraction (EF). Irisin treatment exhibited reduced IL6 and TNF-alpha release in association with less apoptosis, lower muscle injury index and improved survival post-CLP. However, compared to soluble irisin treatment, gold nanoparticles-conjugated to irisin showed a significant improvement in cardiac function, suppression of apoptosis, reduced IL6 and TNF-alpha releases, decreased muscle injury and an improved survival rate of post-CLP. Conclusion: This study reveals that gold nanoparticles-conjugated irisin can serve to improve irisin’s therapeutic effects over a longer course of treatment. National Institute of General MedicalSciences (R01GM 141339); National Heart, Lung, andBlood Institute Grants (R01 HL089405). 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.

Reprogramming cardiac macrophages with circular RNAs to attenuate post-MI adverse remodeling

Cardiac macrophages (cMφ) play a critical role in cardiac remodeling following myocardial infarction (MI). Reprogramming cMφ towards a favorable wound-healing phenotype is emerging as a promising therapeutic strategy for MI patients. Circular RNAs (circRNAs) are a unique class of non-coding RNAs with high stability and abundance, making them attractive therapeutic targets. However, the role of circRNAs in cMφ physiology during heart failure (HF) progression is poorly understood. To identify circRNAs as key regulators of cMφ dynamics, we performed RNA sequencing and bioinformatics analysis on heart biopsies from healthy donors and patients with ischemic HF. We identified a promising circRNA, circMJ1, as a regulator of Mφ polarization and inflammatory response. CircMJ1 was highly expressed in cMφ and its expression was associated with cMφ polarization. Knockdown of circMJ1 significantly inhibited inflammatory signaling pathways in cMφ and reduced the secretion of pro-inflammatory cytokines. The secretome from circMJ1-silenced cMφ (circMJ1-KD cMφ) also significantly suppressed the migration of cardiac fibroblasts and apoptosis of cardiomyocytes. To further assess the therapeutic effcacy of circMJ1-KD Mφ in cardiac remodeling in the context of MI, we employed a novel multicellular 3D ex vivo model, called living myocardial slices (LMS). We applied circMJ1-KD Mφ to both rat LMS subjected to cryo-injury mimicking MI and HF patient-derived LMS. Interestingly, co-culture with circMJ1-KD Mφ demonstrated a remarkable reduction in inflammation and fibrosis, alongside notable improvement in cardiac function in both cryo-injured rat LMS and HF patient-derived LMS. Overall, our findings reveal circMJ1 as a crucial "switch" for Mφ dynamics and suggest the therapeutic potential of engineered circMJ1-silenced Mφ to improve post-MI healing. Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) –465131031. 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.

COMPARISON OF CARDIAC STRUCTURAL AND FUNCTIONAL CHANGES BETWEEN SURGERY AND MEDICATION TREATMENT IN PATIENTS WITH PRIMARY ALDOSTERONISM BASED ON ECHOCARDIOGRAPHY

Objective: Conducted a systematic meta-analysis on the changes in follow-up parameters of echocardiography in patients with primary aldosteronism after surgery and drug treatment, in order to explore their differences. Design and method: We conducted the PubMed, Embase, and Cochrane library databases for English full-text articles on the follow-up study of echocardiography parameters in PA patients before and after surgery and drug treatment published from its establishment until June 1, 2023,Perform meta-analysis on the included studies using RevMan software. Results: A total of 515 PA patients (>18 years old) were included in 4 studies, including the surgical group (n=303) and the medication group (n=212), 2 short-term follow-up studies (average follow-up time of 1 year), and 2 long-term follow-up studies (average follow-up time of 3.7 years). Surgery treatment had better performance in improving cardiac contractile function, The main manifestation is the reversal of left ventricular hypertrophy (LVMI: M=-2.6, p=0.047), while there is no significant improvement in cardiac diastolic function (E/A: M=+0.06, p=0.51); In long-term follow-up studies, surgery and medical treatment still showed significant benefits in reducing blood pressure (surgical group: -14 ± 6 mm Hg/-9 ± 10 mm Hg, p<0.001; drug group: -10 ± 12mmHg/-11 ± 9mmHg, p<0.001). Interestingly, the surgical group and drug group did not show better blood pressure control effects than short-term follow-up (p=0.56), Surgery (LVMI: M=-12.6, p=0.01)and medication (LVMI: M=-11.9, p=0.01])can significantly improve left ventricular hypertrophy in patients, with no significant difference (P=0.143). Although surgery (E/A: M=+0.14, p=0.125) and medication (E/A: M=+0.09, p=0.2) can numerically improve diastolic function, there is no statistically significant difference. Conclusions: Both medication and surgical treatment can reverse the damage to the heart structure and function in PA patients. In the short term, surgical treatment has a more significant reversal of cardiac function, especially in left ventricular hypertrophy, but in the long term, there is no significant difference between medication and surgical treatment.

Setmelanotide Administration Improves Cardiac Systolic Function in Sirtuin-3 Deficient Mice

We previously showed that activation of the brain leptin-melanocortin system, particularly melanocortin-4 receptors (MC4R), markedly improves cardiac function in experimental models of heart failure (HF) via mechanisms that are still poorly understood. Sirtuin 3 (Sirt3) is an important regulator of mitochondrial oxidative phosphorylation and deficiency of Sirt3 has been implicated in cardiovascular diseases. We recently found increased Sirt3 expression as well as increased levels of NAD+, the main Sirt3 activator, in cardiomyocytes of rats treated with chronic intracerebroventricular infusion of leptin at a dose that does not spill over into the systemic circulation. Therefore, we hypothesized that stimulation of Sirt3 activity is required for the improvement of cardiac function during activation of the brain leptin-MC4R axis. To test this hypothesis, we first examined if chronic MC4R activation, using an MC4R agonist, setmelanotide, improves cardiac function in naïve Sirt3-deficient (Sirt3-KO) mice. Baseline cardiac function was assessed by echocardiography (VisualSonics-VEVO3100®) in male and female Sirt3-KO and wild-type (WT) control mice (n=5/group) at 20 weeks of age, and then weekly during setmelanotide treatment (2 mg/kg/day — i.p. via osmotic minipump model 1002) for 3 weeks. Chronic MC4R activation with setmelanotide transiently reduced food intake in both groups and promoted weight loss in Sirt3-KO mice. Setmelanotide treatment improved systolic function in WT mice as evidenced by increases in ejection fraction and fractional shortening (EF: 52.8±4.4 vs. 72.4±4.4%; FS: 26.9±2.7 vs. 42.8±6.4%, for baseline vs. week 3, respectively) and other measures of systolic function including circumferential and longitudinal strains. Despite showing a tendency for reduced systolic function compared to WT controls at baseline, Sirt3-KO mice also exhibited improvement in systolic function with setmelanotide administration (EF: 44.1±1.8 vs. 65.3±2.9% and FS: 21.4±1.0 vs. 35.1±2.1%). No major changes were observed in measures of diastolic function. These results suggest that in a non-HF model, MC4R activation does not require stimulation of Sirt3 to improve indices of systolic function. (1R01HL163076, 1R01DK121411, P20GM104357, P30GM149404, U54GM115428, and AHA-835218). 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.

ITGAM: A Pivotal Regulator in Macrophage Dynamics and Cardiac Function During Sepsis-Induced Cardiomyopathy.

Sepsis-induced cardiomyopathy (SIC) is a critical complication arising from sepsis characterized by reversible myocardial dysfunction. Despite the increasing attention to SIC in research, the underlying molecular mechanisms remain poorly comprehended. In this study, we utilized bioinformatics to analyze RNA-sequencing (RNA-seq) and single-cell RNA-sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database to identify key immune cell populations and molecular markers associated with SIC. Our experimental approach combined in vitro and in vivo studies to investigate the roles of integrin alpha M(ITGAM) and intracellular adhesion molecule-1(ICAM-1) in macrophage recruitment and phenotypic polarization, as well as their impact on cardiac function during SIC. The bioinformatics analysis disclosed significant alterations in gene expression and immune cell composition within the cardiac tissue during SIC, where macrophages emerged as the predominant immune cell type. Notably, ITGAM was identified as a key regulatory molecule that modulates macrophage function, driving the pathogenesis of SIC through its influence on the recruitment and functional reprogramming of these cells. In vitro experiments revealed that lipopolysaccharide (LPS) stimulation triggered an upregulation of ITGAM in macrophages and ICAM-1 in endothelial cells, underscoring their critical roles in immune cell mobilization and intercellular communication. The strategic administration of ITGAM-neutralizing antibodies to SIC mice resulted in a marked decrease in macrophage infiltration within the cardiac tissue, which was initially associated with an improvement in cardiac function. However, this intervention paradoxically resulted in an increased mortality rate during the later phases of SIC, underscoring the complex and dualistic function of ITGAM. This study provides new insights into the complex dynamics of immune cells within the cardiac environment during SIC, with a particular emphasis on the modulatory role of ITGAM in shaping macrophage behavior. The findings shed light on the reversible nature of myocardial dysfunction in SIC and emphasize the importance of targeted therapeutic strategies for the effective management of SIC.

Exploring the Efficacy Enhancement Mechanism of Qixue Shuangbu prescription after TCM processing for treating chronic heart failure by regulating ERK/Bcl-2/Bax/Caspases-3 signaling pathway

Qixue Shuangbu prescription (QSP) has been used for the treatment of chronic heart failure (CHF) with remarkable curative effect. Processed QSP (PQSP) could significantly improve the treatment of CHF after traditional Chinese medicine (TCM) processing. This study elucidated the underlying efficacy enhancement mechanism of QSP after TCM processing for treating CHF in vitro and in vivo. The injury of rat cardiomyoblast H9c2 cells was induced by anoxia/reoxygenation to mimic CHF state in vitro. Sixty Sprague-Dawley rats were used to established CHF model by intraperitoneally injecting doxorubicin (the accumulative dose 15 mg/kg). Biochemical examinations were performed in serum and cellular supernatant, respectively. Cardiac functions and histopathological changes were evaluated in CHF model rats. The protein and mRNA levels of ERK1/2, Bcl-2, Bax and Caspase-3 were evaluated by Western blot and RT-PCR, respectively. All above results of low dose crude QSP-treated group (L-CQSP), high dose CQSP-treated group (H-CQSP), low dose PQSP-treated group (L-PQSP), high dose PQSP-treated group (H-PQSP) were compared to systematically explore correlations between TCM processing and the efficacy enhancement for treating CHF of PQSP. Compared with the model group, the L-CQSP group showed significant improvement in cardiac function at 8th weeks, while no significant improvement in cardiomyocyte apoptosis and fibrosis. Both H-CQSP, L-PQSP and H-PQSP exerted beneficial therapeutic effects in injured H9c2 cardiomyocytes and CHF model rats. L-PQSP and H-PQSP significantly increased cell viability and the activity of SOD, decreased the activities of LDH, MDA and NO, up-regulated the expression of ERK1/2 and Bcl-2, down-regulated the expression of Bax and Caspase-3 compared to the same dosage of CQSP. The efficacy enhancement mechanism of PQSP after TCM processing for treating CHF was directly related to the regulation of ERK/Bcl-2/Bax/Caspases-3 signaling pathway.

Cardioprotection and Suppression of Fibrosis by Diverse Cancer and Non-Cancer Cell Lines in a Murine Model of Duchenne Muscular Dystrophy.

The dynamic relationship between heart failure and cancer poses a dual challenge. While cardiac remodeling can promote cancer growth and metastasis, tumor development can ameliorate cardiac dysfunction and suppress fibrosis. However, the precise mechanism through which cancer influences the heart and fibrosis is yet to be uncovered. To further explore the interaction between heart failure and cancer, we used the MDX mouse model, which suffers from cardiac fibrosis and cardiac dysfunction. A previous study from our lab demonstrated that tumor growth improves cardiac dysfunction and dampens fibrosis in the heart and diaphragm muscles of MDX mice. We used breast Polyoma middle T (PyMT) and Lewis lung carcinoma (LLC) cancer cell lines that developed into large tumors. To explore whether the aggressiveness of the cancer cell line is crucial for the beneficial phenotype, we employed a PyMT breast cancer cell line lacking integrin β1, representing a less aggressive cell line compared to the original PyMT cells. In addition, we examined immortalized and primary MEF cells. The injection of integrin β1 KO PyMT cancer cells and Mouse Embryo Fibroblasts cells (MEF) resulted in the improvement of cardiac function and decreased fibrosis in the heart, diaphragm, and skeletal muscles of MDX mice. Collectively, our data demonstrate that the cancer line aggressiveness as well as primary MEF cells are sufficient to impose the beneficial phenotype. These discoveries present potential novel clinical therapeutic approaches with beneficial outcome for patients with fibrotic diseases and cardiac dysfunction that do not require tumor growth.

Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER

PurposeEvaluate long-term efficacy and safety of elamipretide during the open-label extension (OLE) of the TAZPOWER trial in individuals with Barth syndrome (BTHS). MethodsTAZPOWER was a 28-week randomized, double-blind, and placebo-controlled trial followed by a 168-week OLE. Patients entering the OLE continued elamipretide 40 mg subcutaneous daily. OLE primary endpoints were safety and tolerability; secondary endpoints included change from baseline in the 6-minute walk test (6MWT) and BarTH Syndrome Symptom Assessment (BTHS-SA) Total Fatigue. Muscle strength, physician- and patient-assessed outcomes, echocardiographic parameters, and biomarkers, including cardiolipin (CL) and monolysocardiolipin (MLCL), were assessed. ResultsTen patients entered the OLE; 8 reached the week 168 visit. Elamipretide was well tolerated, with injection-site reactions being the most common adverse events. Significant improvements from OLE baseline on 6MWT occurred at all OLE time points (cumulative 96.1 m of improvement [week 168, P = .003]). Mean BTHS-SA Total Fatigue scores were below baseline (improved) at all OLE time points. Three-dimensional (3D) left ventricular stroke, end-diastolic, and end-systolic volumes improved, showing significant trends for improvement from baseline to week 168. MLCL/CL values showed improvement, correlating to important clinical outcomes. ConclusionElamipretide was associated with sustained long-term tolerability and efficacy, with improvements in functional assessments and cardiac function in BTHS.

(155) - Defining Optimal Criteria for LVAD Weaning in HF Patients with an Improvement in Cardiac Structure and Function: A VAD Wean Registry Analysis

(155) - Defining Optimal Criteria for LVAD Weaning in HF Patients with an Improvement in Cardiac Structure and Function: A VAD Wean Registry Analysis

Semaglutide attenuates doxorubicin-induced cardiotoxicity by ameliorating BNIP3-Mediated mitochondrial dysfunction

AimsDoxorubicin is a powerful chemotherapeutic agent for cancer, whose use is limited due to its potential cardiotoxicity. Semaglutide (SEMA), a novel analog of glucagon-like peptide-1 (GLP-1), has received widespread attention for the treatment of diabetes. However, increasing evidence has highlighted its potential therapeutic benefits on cardiac function. Therefore, the objective of this study was to examine the efficacy of semaglutide in ameliorating doxorubicin-induced cardiotoxicity. Methods and resultsDoxorubicin-induced cardiotoxicity is an established model to study cardiac function. Cardiac function was studied by transthoracic echocardiography and invasive hemodynamic monitoring. The results showed that semaglutide significantly ameliorated doxorubicin-induced cardiac dysfunction. RNA sequencing suggested that Bnip3 is the candidate gene that impaired the protective effect of semaglutide in doxorubicin-induced cardiotoxicity. To determine the role of BNIP3 on the effect of semaglutide in doxorubicin-induced cardiotoxicity, BNIP3 with adeno-associated virus serotype 9 (AAV9) expressing cardiac troponin T (cTnT) promoter was injected into tail vein of C57/BL6J mice to overexpress BNIP3, specifically in the heart. Overexpression of BNIP3 prevented the improvement in cardiac function caused by semaglutide. In vitro experiments showed that semaglutide, via PI3K/AKT pathway, reduced BNIP3 expression in the mitochondria, improving mitochondrial function. ConclusionSemaglutide ameliorates doxorubicin-induced mitochondrial and cardiac dysfunction via PI3K/AKT pathway, by reducing BNIP3 expression in mitochondria. The improvement in mitochondrial function reduces doxorubicin-mediated cardiac injury and improves cardiac function. Therefore, semaglutide is a potential therapy to reduce doxorubicin-induced acute cardiotoxicity.

Cardiac remodeling in patients with atrial fibrillation reversing bradycardia-induced cardiomyopathy: A case report

BACKGROUND Bradycardia-induced cardiomyopathy (BIC), which is a disease resulting from bradycardia, is characterized by cardiac chamber enlargement and diminished cardiac function. The correction of bradycardia can allow for significant improvements in both cardiac function and structure; however, this disease has been infrequently documented. In this case, we conducted a longitudinal follow-up of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention. CASE SUMMARY A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7. Since she had no obvious symptoms, she did not receive any treatment to improve her bradycardia during the 42-year follow-up, except for the implantation of a temporary pacemaker during labor induction surgery. As time progressed, the patient's heart gradually expanded due to her low ventricular rate, and she was diagnosed with BIC. In 2014, the patient developed atrial fibrillation, her ventricular rate gradually increased, and her heart shape gradually returned to normal. This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years, introduces another possible outcome of BIC, and emphasizes the importance of early intervention in treating BIC. CONCLUSION BIC can induce atrial fibrillation, causing an increased ventricular rate and leading to positive cardiac remodeling.

Treatment of a Pial Arterial Venous Fistula in a Newborn: 2-Dimensional Operative Video.

Pial arterial venous fistulas (PAVFs) are rare vascular entities that occur with direct high-flow connections between pial arterial feeders and large veins without an intervening nidus.1-5 These vascular abnormalities can present in the pediatric population with high output heart failure.1 PAVFs can be treated with endovascular intervention, microvascular ligation, or a combination depending on the clinical scenario.4 Here, we present a case in which a newborn presented in high output heart failure because of a large left-sided middle cerebral artery fed PAVF. We performed a craniotomy for ligation of the PAVF to obliterate the arteriovenous shunting to improve her cardiac status and diminish her intracranial venous hypertension. Throughout the ligation, we used indocyanine green to localize the next appropriate vessels to ligate, allowing us to safely obliterate the anomalous vasculature and improve the patient's cardiac function. Postoperatively, the patient did well neurologically with improvements in cardiac function and near normalization of intracranial vasculature. The patient's guardians consented to the procedure and to the publication of her image.

Efficacy of physical exercise on the physical ability, cardiac function and cardiopulmonary fitness of patients with atrial fibrillation: a systematic review and meta-analysis.

It is advised that patients engage in physical activity to enhance their quality of life and achieve better results. The purpose of the current study was to measure the efficacy of exercise on the physical ability, cardiac function and cardiopulmonary fitness of patients with AF. A comprehensive systematic literature search was performed in PubMed, Embase, and Web of Science from 1991 to 2023 for RCTs comparing physical exercise combined with AF routine treatments to routine treatments alone. The meta-analysis was conducted following PRISMA guidelines. Our main outcomes were physical ability (measured by the 6-min walk test, 6MWT), cardiac function (measured by left ventricular ejection fraction, LVEF) and cardiopulmonary fitness (measured by peak oxygen uptake and resting heart rate). Quality assessments were conducted using the Cochrane Collaboration tool. Thirteen trials involving 672 patients met the criteria for analysis. The results showed that physical exercise increased physical ability by improving the 6MWT (m) performance (MD = 96.99, 95% CI: 25.55-168.43; Z = 2.66; p = 0.008); and enhanced peak VO2 (ml/kg per min) (MD = 4.85, 95% CI: 1.55-8.14; Z = 2.89; p = 0.004) while reducing resting heart rate (beats per minute, bpm) (MD = -6.14, 95% CI: -11.30 to -0.98; Z = 2.33; p = 0.02). However, the results showed that regular exercise could improve LVEF (%) inpatients clinically, which had no statistic difference between experimental and control group (MD = 1.49, 95% CI: -0.25-3.24; Z = 1.68; p = 0.09). Our meta-analysis shows that physical exercise is an effective intervention to improve the exercise ability and cardiopulmonary fitness for AF patients. Meanwhile, we also do not exclude the positive effect of exercise on the improvement of cardiac function (LVEF) in patients with AF. To this end, doctors should consider the positive impact of exercise on patients and give advice on exercise limits in practical clinical practice.

CircPAN3/miR-221/PTEN axis and apoptosis in myocardial Infarction: Quercetin's regulatory effects

The circular RNA/microRNA/mRNA axis is a new layer of non-coding RNA(ncRNA)-based regulatory gene expression networks upstream of numerous cell signaling pathways. Circular RNAPAN3 (circPAN3) is involved in autophagy, fibrosis and apoptosis which are responsible for the reduction incardiac functional capacityfollowingmyocardial infarction(MI). However, the molecular mechanism of circPAN3 association with apoptosis is unknown. In addition, the relationship between quercetin as a cardioprotective factor in MI and circular RNA-dependent regulatory pathways has not yet been elucidated. MI was induced in Wistar rats using the left anterior descending artery (LAD) ligation method. One day after surgery, quercetin (30 mg/kg) was injected intraperitoneal (IP) every other day for two weeks. The expression of circPAN3 was increased in the MI group (P < 0.05). The increase in circPAN3 was accompanied by a decrease in miR-221 (P < 0.0001), an increase in PTEN (P < 0.0001), and cleaved caspase 3 (P < 0.001). Quercetin effectively reduced the expression of circPAN3 (P < 0.05), PTEN (P < 0.0001), and cleaved caspase 3 (P < 0.001), and increased the expression of miR-221 (P < 0.0001) and the ratio of p-AKT to p-PI3K (P < 0.001). The circPAN3/miR-221/PTEN pathway is an ncRNA-dependent apoptotic pathway in MI cardiac tissue. Quercetin effectively modulated this pathway, resulting in a reduction of cardiac tissue death and improvement in cardiac function after MI. This suggests that the circPAN3/miR-221 axis plays a role in apoptosis in MI, and quercetin can act as a protective candidate by modulating this pathway.

A fibrin patch loaded with mesenchymal stem cells-derived exosomes improves cardiac functions after myocardial infarction

Myocardial infarction (MI) is a typical cardiovascular disease, causing disability and death worldwide. Exosomes secreted by mesenchymal stem cells (MSCs) showed remarkable therapeutic effects in MI by restoring cardiac function. However, the application of exosomes remains a challenge because of their low residence rate in the infarcted myocardium. Herein, a fibrin-based cardiac patch was prepared to deliver MSCs-derived exosomes to the infarcted heart using an MI mouse model, aiming at improvement of cardiac functions. The fibrin patch was optimized for size to minimize the mouse mortality rate. The composite patch showed sustained release of exosomes in vitro and could improve the retention of exosomes in the infarcted heart, inhibiting fibrosis and improving cardiac functions in vivo. Therefore, this combination of natural biomaterial-based cardiac patch and MSCs-derived exosomes may have a promising clinical translational potential for the MI treatment.

Early postoperative constrictive pericarditis in China: a single-center retrospective observational study.

The diagnosis, treatment, and prognosis of early postoperative constrictive pericarditis (EPCP) have not been discussed in depth. The objective of this study was to devise and propose a management strategy for EPCP. In this study, constrictive pericarditis (CP) within 6 months after cardiac surgery was defined as EPCP, and patients were divided into two groups based on intraoperative findings: a parietal thickening group and a visceral thickening group. A total of 20 patients were included in this study, and the incidence rate of recurrent pericardiectomy was 0.32% among all patients undergoing cardiovascular surgery. EPCP after valve surgery occurred in 85.0% of patients. Pleural effusion was the most common preoperative symptom, occurring in 90% of patients. Pericardial thickening occurred in the visceral layer in seven cases and in the parietal layer in 13 cases. There were no differences in comorbidities, C-reactive protein (CRP) level, or erythrocyte sedimentation rate (ESR) between the two groups. Most patients with visceral thickening (83.3%) needed cardiopulmonary bypass (CPB) assistance during surgery and had a longer hospital stay than those with parietal thickening (52.8±21.8 vs. 34.9±13.8 days, P=0.049). Central venous pressure (CVP) was decreased in all patients after pericardiectomy (24.9±6.96 vs. 8.9±2.92 cmH2O, P<0.001), and the cardiac function improved significantly in patients with parietal thickening [New York Heart Association (NYHA) grade ≥ III accounted for 28.6% of patients]. The long-term survival rate of patients with parietal thickening was 92.3% and that of patients with visceral thickening was 57.1%, and there was no significant difference between them (P=0.056). Recurrent episodes of chest tightness, pleural effusion, and elevated CVP within 6 months after cardiac surgery should be considered highly suggestive of EPCP. There are few points of difference between pericarditis with thickening of the parietal and visceral layers. After failure of conservative medical treatment, pericardiectomy results in significant improvements in cardiac function and quality of life, especially in patients with thickening of the parietal layer.

Proteomic Analysis and Sex-Specific Changes in Chronically Ischemic Swine Myocardium Treated with Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin.

Although sodium-glucose cotransporter-2 inhibitors have been shown to improve cardiovascular outcomes in general, little is presently known about any sex-specific changes that may result from this therapy. We sought to investigate and quantify potential sex-specific changes seen with the sodium-glucose cotransporter-2 inhibitor canagliflozin (CAN) in a swine model of chronic myocardial ischemia. Eighteen Yorkshire swine underwent left thoracotomy with placement of an ameroid constrictor. Two weeks postop, swine were assigned to receive either control (F = 5 and M = 5) or CAN 300 mg daily (F = 4 and M = 4). After 5 weeks of therapy, swine underwent myocardial functional measurements, and myocardial tissue was sent for proteomic analysis. Functional measurements showed increased cardiac output, stroke volume, ejection fraction, and ischemic myocardial flow at rest in male swine treated with CAN compared with control male swine (all p < 0.05). The female swine treated with CAN had no change in cardiac function as compared with control female swine. Proteomic analysis demonstrated 6 upregulated and 97 downregulated proteins in the CAN female group compared with the control female group. Pathway analysis showed decreases in proteins in the tricarboxylic acidic cycle. The CAN male group had 639 upregulated and 172 downregulated proteins compared with control male group. Pathway analysis showed increases in pathways related to cellular metabolism and decreases in pathways relevant to the development of cardiomyopathy and to oxidative phosphorylation. Male swine treated with CAN had significant improvements in cardiac function that were not observed in female swine treated with CAN. Moreover, CAN treatment in male swine was associated with significantly more changes in protein expression than in female swine treated with CAN. The increased proteomic changes seen in the CAN male group likely contributed to the more robust changes in cardiac function seen in male swine treated with CAN.

The evaluation of bariatric surgery effect on cardiac structure and function using transthoracic echocardiography: a cohort study

BackgroundObesity is a pathology and a leading cause of death worldwide. Obesity can harm multiple organs, including the heart. In this study, we aim to investigate the effect of bariatric surgery and following weight loss on cardiac structure and functions using echocardiography parameters in patients with morbid obesity.MethodsIn this cohort study, 30 patients older than 18 with BMI > 40 or BMI > 35 and comorbidity between March 2020 to March 2021 were studied. The patients underwent transthoracic echocardiography before and after six months of the bariatric surgery.ResultsIn total, 30 patients (28 women, 93.3%) with a mean age of 38.70 ± 9.19 were studied. Nine (30%) were diabetic, and 9 (30%) had hypertension. After six months of bariatric surgery, all physical measurements, including weight, Body mass index, and Body surface area, decreased significantly (p < 0.001). After bariatric surgery, all parameters regarding left ventricular morphology, including left ventricular mass, interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-systolic diameter, and left ventricular end-diastolic diameter, improved significantly (p < 0.001). Also, LVEF rose post-bariatric surgery (p < 0.001). TAPSE parameter indicating right ventricular function also improved (p < 0.001). Right ventricular diameter, left atrium volume, and mitral inflow E/e’ decreased significantly (p < 0.001).ConclusionSystolic and diastolic parameters refine significantly after bariatric surgery in patients with obesity. Bariatric surgery lead to significant cardiac structure and function improvement.