Improvement In Ventricular Function Research Articles

Effect of phosphodiesterase type 5 inhibitors on surgical outcome of ventricular septal defect and pulmonary hypertension patients

BackgroundChildren with ventricular septal defect (VSD) and large systemic-to-pulmonary shunts eventually develop pulmonary hypertension (PH). The perioperative management of patients with VSD and PH is quite troublesome and still debatable, especially in developing countries where the different management options and standardization of treatment is not available. Oral phosphodiesterase type 5 (PDE-5) inhibitors are good treatment options being widely available, cheap, easy administration and do not require extensive monitoring. The aim of our study was to evaluate the effect of the PDE-5 inhibitors when given orally, early preoperative and continued for 3 months postoperative on controlling postoperative PH with its effect on right ventricle (RV) functions. Fifty-one patients were randomly assigned to either sildenafil or tadalafil, 1 week before and continued for 3 months after corrective surgery. The control group received a placebo.ResultsThere was no significant difference in the improvement in the right ventricle systolic pressure (RVSP) between both groups, early in the postoperative period (P = 0.255) and in follow-up (P = 0.259). There was also no significant difference in the changes in mean pulmonary artery pressure (mPAP), postoperatively and on follow-up (P = 0.788 and 0.059, respectively). There was a drop in RV functions in both groups postoperatively which improved on follow-up; however, it was not significant between both groups. The length of intensive care unit (ICU) stay was similar between both groups (P = 0.143).ConclusionPerioperative administration of PDE-5 inhibitors does not have an impact on the clinical course as regards improvement in pulmonary artery (PA) pressure, ventricular functions and ICU stay.

Improvement in Left Ventricular Function of the Resected Myocardium after Septal Myectomy in Patients with Aortic Valve Replacement

Background: Some surgeons have previously advocated for a more aggressive concomitant septal myectomy to address left ventricular outflow tract obstruction; however, concerns about the surgical complications of post-septal myectomy remain. Here, we aimed to assess the clinical, echocardiographic, and pathological findings following concomitant septal myectomy with surgical aortic valve replacement. Methods: We reviewed 21 patients who underwent surgical aortic valve replacement and concomitant septal myectomy from April 2014 to September 2019. The global and regional left ventricular ejection fraction changes between the perioperative periods were analyzed using two-dimensional speckle-tracking echocardiography. The resected myocardium was pathologically assessed. Results: No operative mortality was observed during the study period. Transthoracic echocardiography showed no significant differences in preoperative and postoperative left ventricular ejection fraction (68.1 ± 9.9% vs. 68.6 ± 6.0%, p = 0.82) or interventricular septum thickness (11.9 ± 1.4 mm vs. 11.5 ± 1.5 mm, p = 0.23). Interventricular septum thickness at the end-systolic phase, which is the maximum septal wall thickness, was significantly reduced postoperatively (27.7 ± 9.3 mm vs. 22.6 ± 5.5 mm, p < 0.05). The basal, mid, and apical septal areas improved with septal myectomy by 80%, 230%, and 27%, respectively, compared to perioperative echocardiography (basal septal, 80 ± 23%; mid septal, 230 ± 830%; apical septal, 27 ± 350%). Pathological examination of the resected myocardium revealed marked endocardial thickness (mean, 914 µm) with focal fibrosis. Conclusions: In aortic valve stenosis patients with septal hypertrophy, concomitant septal myectomy with surgical aortic valve replacement improved regional myocardial function and eliminated left ventricular outflow tract obstruction by removing thickened endocardium and prominent fibrosis.

Reperfusion therapies in patients with intermediate- and high-risk pulmonary embolism: insights from a multicenter registry

Abstract Funding Acknowledgements None. Background Most acute pulmonary embolism (PE) patients receive anticoagulation as a sole treatment. Reperfusion therapies are required in high-risk (HR) and in intermediate-risk (IR)-PE patients with clinical deterioration. Systemic thrombolysis (ST) is the first-line reperfusion therapy, but due to contraindications and major bleeding concerns, catheter-directed therapies (CDT) are rising as a suitable alternative. Purpose The main objective of this study was to look for predictors that lead physicians to decide between different PE therapies in a contemporary cohort of patients. Methods This ambispective registry included consecutive IR- and HR-acute PE patients evaluated by local Pulmonary Embolism Response Team in two tertiary centers from 2014 to 2022. The patients were grouped according to the elected therapy: anticoagulation alone, CDT or ST. If more than one reperfusion therapy was used, the patient was assigned to the group of the first administered therapy. Predictors of reperfusion therapy assignment were evaluated using a logistic regression analysis. Also, early safety outcomes and procedural results after CDT were analyzed. Results A total of 274 patients were included. Of them, 112 received only anticoagulation, 96 received ST as primary treatment, and 66 underwent CDT at first. Baseline characteristics are displayed in Picture 1. Patients in the ST group were significantly younger (p<0.01). Comorbidities were higher in the CDT group compared to the other two. Patients undergoing CDT or ST had higher PE severity parameters at hospital admission than the anticoagulation group (e.g. shock index, RV involvement, or lactate levels; p<0.01 for all). The Pulmonary Embolism Severity Index score, which incorporates comorbidities and PE severity parameters, was higher in CDT patients compared to the other two groups (p<0.01). Picture 2 shows the trend in the choice between the two primary reperfusion therapies over the years. After multivariable analysis, the Charlson comorbidity index, recent surgery and bilateral central PE remained independent predictors for the use of CDT instead of ST (p<0.05 for all). A significant decrease in the systolic and mean pulmonary artery pressure and a significant increase in systolic blood pressure after procedure was detected in patients undergoing CDT. Regarding early safety outcomes, intracranial bleeding occurred only in the ST group. In contrast, the incidence of major bleeding, acute kidney injury and 30-day mortality did not differ between CDT and ST groups. Conclusion This contemporary registry used CDT as primary therapy in 24% of IHR and HR patients, mainly in comorbid and post-surgical patients, and increased over time. CDT was a safe and effective alternative to ST, achieving significant and early improvement in right ventricular function and hemodynamics.Baseline characteristicsChoice of reperfusion therapy over time

Atrial Septal Defect Closure: Not Always Straightforward.

A nine-year old boy presented following a chest x-ray for COVID-19 infection that showed cardiomegaly. Transthoracic echocardiogram revealed a large atrial septal defect, dilated right heart, and normal function. Surgical repair was performed eight weeks after his COVID diagnosis. After weaning from cardiopulmonary bypass, pulmonary artery pressures were 2/3 systemic and ectopy was seen, requiring inotropes, nitric oxide, lidocaine, and amiodarone. He was discharged on postoperative day (POD) 5. On POD 6, he presented with acute right foot ischemia. Computed tomography showed a large aortic thrombus, requiring emergent thrombectomy. Coagulopathy workup was negative. Cardiac magnetic resonance imaging (CMR) and catheterization showed reduced biventricular function and diastolic dysfunction. Diuretics and β blockers were started, with gradual improvement in left ventricular systolic function.

Sacubitril/valsartan has an underestimated impact on the right ventricle in patients with sleep-disordered breathing, especially central sleep apnoea syndrome

BackgroundSacubitril/valsartan has been demonstrated to significantly improve left ventricular performance and remodelling in patients with heart failure. However, its effects on the right ventricle in patients with chronic heart failure and sleep-disordered breathing (SDB) have not been studied. AimTo investigate the impact of sacubitril/valsartan treatment on right ventricular function in patients with SDB. MethodsThis was a subanalysis of an observational prospective multicentre study involving 101 patients. At inclusion, patients were evaluated by echocardiography and nocturnal ventilatory polygraphy, which allowed patients to be divided into three groups: “central-SDB”; “obstructive-SDB”; and “no-SDB”. ResultsAfter 3 months of sacubitril/valsartan therapy, a positive impact on right ventricular function was observed. In the general population, tricuspid annular plane systolic excursion increased by +1.32±4.74mm (P=0.024) and systolic pulmonary artery pressure decreased by −3.1±10.91mmHg (P=0.048). The central-SDB group experienced the greatest echocardiographic improvement, with a significant increase in tricuspid annular plane systolic excursion of +2.1±4.9mm (P=0.045) and a significant reduction in systolic pulmonary artery pressure of −8.4±9.7mmHg (P=0.001). ConclusionsSacubitril/valsartan improved right ventricular function in patients with heart failure and SDB after only 3 months of treatment. The greatest improvement in right ventricular function was observed in the central-SDB group.

Effects of sacubitril/valsartan versus olmesartan on left atrial structure in hypertensive patients without HFrEF: a randomized controlled trial

Background and purpose: Treatment with sacubitril plus valsartan attenuates cardiac remodeling in patients with heart failure with reduced ejection fraction (HFrEF). Evidence for potential effects of sacubitril/valsartan on left atrial remodeling in hypertensive patients without HFrEF, however, is limited. Therefore, we aimed to compare the effects of sacubitril/valsartan and olmesartan on the left atrial structure in Chinese hypertensive patients. Methods: This single-center randomized controlled trial was conducted at Nanjing First Hospital from June 2021 to February 2022. Adult patients (18–80 years of age) with essential hypertension but no HFrEF were randomized at a 1:1 ratio to receive sacubitril/valsartan or olmesartan. Initial dosage was 100 mg/day for sacubitril/valsartan and 20 mg/day for olmesartan. In patients who did not reach the target blood pressure (<140/90 mmHg) within a week, dosage was increased to 200 to 400 mg/day for sacubitril/valsartan and 40 mg/day for olmesartan. In patients who failed to reach the target blood pressure at 4 weeks, other antihypertensive drugs were used at physician’s discretion. The patients should reach the target blood pressure at 8 weeks. The primary endpoint was the change of left atrial volume index (LAVI) from baseline to 24 weeks. Secondary endpoints included the changes of left atrial diameter (LAD), left atrial emptying fraction (LAEF), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic diameter (LVEDD) from baseline to 24 weeks. Results are shown as median and interquartile range (IQR). Results: A total of 153 patients were enrolled. The final analysis included 145 patients who completed the 24-week assessment: 71 and 74 in the sacubitril/valsartan and olmesartan groups, respectively. Demographic and key baseline characteristics (e.g., blood pressure) were comparable between the 2 groups. Target blood pressure was achieved in all 145 patients at 8 weeks. In comparison to the olmesartan group, the sacubitril/valsartan group had significantly greater change in LAVI (−4.19 [−2.87, −5.43] vs. −0.61 [−0.53, −1.13] mL/m2, P < 0.001), LAEF (1.00% [2.00%, 0%] vs. 0% [1.00%, −1.00%], P = 0.014), LVEDD (−2.00 [0, −3.00]mm vs. −1.00 [0, −1.00]mm, P < 0.001), and LVEF (1.00% [3.00%, 1.00%] vs. 0% [1.00%, 0%], P < 0.001), but not LAD, LAVI, LAEF, LVEDD, and LVEF at 24 weeks relative to the baseline. Conclusions: In comparison to olmesartan, sacubitril/valsartan resulted in more robust improvements in left atrial and ventricular structure and function in hypertensive patients without HFrEF.

Cholinergic Stimulation Exerts Cardioprotective Effects and Alleviates Renal Inflammatory Responses after Acute Myocardial Infarction in Spontaneous Hypertensive Rats (SHRs).

In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). Adult male SHRs were randomized into three experimental groups: sham-operated; AMI + Veh (infarcted, treated with vehicle); and AMI + PY (infarcted, treated with the cholinesterase inhibitor, pyridostigmine bromide (PY)-40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. The clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. Seven days post-surgery, the AMI + PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI + Veh group. Furthermore, there was a notable downregulation in pro-inflammatory gene expression and an upregulation in anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers, indicative of subclinical kidney injury. Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

Clinical features of plastic bronchitis in children after congenital heart surgery

BackgroundPlastic bronchitis (PB) can occur in patients who have undergone congenital heart surgery (CHS). This study aimed to investigate the clinical features of PB in children after CHS.MethodsWe conducted a retrospective cohort study using the electronic medical record system. The study population consisted of children diagnosed with PB after bronchoscopy in the cardiac intensive care unit after CHS from May 2016 to October 2021.ResultsA total of 68 children after CHS were finally included in the study (32 in the airway abnormalities group and 36 in the right ventricular dysfunction group). All children were examined and treated with fiberoptic bronchoscopy. Pathogens were detected in the bronchoalveolar lavage fluid of 41 children, including 32 cases in the airway abnormalities group and 9 cases in the right ventricular dysfunction group. All patients were treated with antibiotics, corticosteroids (intravenous or oral), and budesonide inhalation suspension. Children with right ventricular dysfunction underwent pharmacological treatment such as reducing pulmonary arterial pressure. Clinical symptoms improved in 64 children, two of whom were treated with veno-arterial extracorporeal membrane oxygenation (ECMO) due to recurrent PB and disease progression.ConclusionsChildren with airway abnormalities or right ventricular dysfunction after CHS should be alerted to the development of PB. Pharmacological treatment such as anti-infection, corticosteroids, or improvement of right ventricular function is the basis of PB treatment, while fiberoptic bronchoscopy is an essential tool for the diagnosis and treatment of PB. ECMO assistance is a vital salvage treatment for recurrent critically ill PB patients.

SPECTRA Phase 2b Study: Impact of Sotatercept on Exercise Tolerance and Right Ventricular Function in Pulmonary Arterial Hypertension.

This study aims to assess the impact of sotatercept on exercise tolerance, exercise capacity, and right ventricular function in pulmonary arterial hypertension. SPECTRA (Sotatercept Phase 2 Exploratory Clinical Trial in PAH) was a phase 2a, single-arm, open-label, multicenter exploratory study that evaluated the effects of sotatercept by invasive cardiopulmonary exercise testing in participants with pulmonary arterial hypertension and World Health Organization functional class III on combination background therapy. The primary end point was the change in peak oxygen uptake from baseline to week 24. Cardiac magnetic resonance imaging was performed to assess right ventricular function. Among the 21 participants completing 24 weeks of treatment, there was a significant improvement from baseline in peak oxygen uptake, with a mean change of 102.74 mL/min ([95% CIs, 27.72-177.76]; P=0.0097). Sotatercept demonstrated improvements in secondary end points, including resting and peak exercise hemodynamics, and 6-minute walk distance versus baseline measures. Cardiac magnetic resonance imaging showed improvements from baseline at week 24 in right ventricular function. The clinical efficacy and safety of sotatercept demonstrated in the SPECTRA study emphasize the potential of this therapy as a new treatment option for patients with pulmonary arterial hypertension. Improvements in right ventricular structure and function underscore the potential for sotatercept as a disease-modifying agent with reverse-remodeling capabilities. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03738150.

Transcatheter Aortic Valve Implantation for Aortic Regurgitation: A Comprehensive Review.

Aortic regurgitation (AR), a left-sided valvular heart disease, poses challenges in both diagnosis and treatment. From rheumatic fever to trauma, the vast etiologies of AR can manifest with varying symptoms and disease progression. Nonetheless, without interventions, patients with acute and chronic symptomatic AR have a poor prognosis. This article synthesizes current knowledge on AR management, emphasizing advancements in transcatheter aortic valve implantation (TAVI). While surgical aortic valve replacement remains the gold standard, TAVI has emerged as a promising alternative, particularly for inoperable patients. It is currently used off-label for patients with bicuspid valve and valve-in-valve procedures. Clinical data from various studies underscore TAVI's efficacy in AR, demonstrating improvements in left ventricular function and mortality rates with use of the new-generation devices. However, challenges persist with conditions such as aortic aneurysms, including device positioning and selection. With ongoing technological innovations, TAVI holds potential as a viable option in selected AR patients, necessitating further research for optimized outcomes.

Predictors of improvement in left ventricular systolic function after catheter ablation in patients with persistent atrial fibrillation complicated with heart failure

AimsThe current management of patients with atrial fibrillation (AF) and concomitant heart failure (HF) remains a significant challenge. Catheter ablation (CA) has been shown to improve left ventricular ejection fraction (LVEF) in these patients, but which patients can benefit from CA is still poorly understood. The aim of our study was to determine the predictors of improved ejection fraction in patients with persistent atrial fibrillation (PeAF) complicated with HF undergoing CA.Methods and resultsA total of 435 patients with persistent AF underwent an initial CA between January 2019 and March 2023 in our hospital. We investigated consecutive patients with left ventricular systolic dysfunction (LVEF < 50%) measured by transthoracic echocardiography (TTE) within one month before CA. According to the LVEF changes at 6 months, these patients were divided into an improved group (fulfilling the ‘2021 Universal Definition of HF’ criteria for LVEF recovery) and a nonimproved group. Eighty patients were analyzed, and the improvement group consisted of 60 patients (75.0%). In the univariate analysis, left ventricular end-diastolic diameter (P = 0.005) and low voltage zones in the left atrium (P = 0.043) were associated with improvement of LVEF. A receiver operating characteristic analysis determined that the suitable cutoff value for left ventricular end-diastolic diameter (LVDd) was 59 mm (sensitivity: 85.0%, specificity: 55.0%, area under curve: 0.709). A multivariate analysis showed that LVDd (OR = 0.85; 95% CI: 0.76–0.95, P = 0.005) and low voltage zones (LVZs) (OR = 0.26; 95% CI: 0.07–0.96, P = 0.043) were significantly independently associated with the improvement of LVEF. Additionally, parameters were significantly improved regarding the left atrial diameter, LVDd and ventricular rate after radiofrequency catheter ablation (all p < 0.05).ConclusionsThe improvement of left ventricular ejection fraction (LVEF) occurred in 75.0% of patients. Our study provides additional evidence that LVDd < 59 mm and no low voltage zones in the left atrium can be used to jointly predict the improvement of LVEF after atrial fibrillation ablation.

Modern physiological approach to inappropriate ICD shocks due to atrial fibrillation with very fast ventricular response. A case report

BackgroundFast-conducting atrial fibrillation misinterpreted as ventricular tachycardia is the leading cause for inappropriate shocks in patients with implantable cardiac defibrillators (ICD). These inappropriate shocks are associated with significant morbidity and mortality and cause great discomfort and stress.Case presentationWe report the case of a patient with ischemic cardiomyopathy, permanent atrial fibrillation, and a single-chamber DF-1 ICD implanted for the primary prevention of sudden cardiac death, who presented for multiple inappropriate internal shocks due to very fast-conducting atrial fibrillation, which was mislabeled as ventricular fibrillation by the ICD. Since the patient was under maximal atrioventricular nodal blocking medical therapy (beta-blockers and digitalis) and we didn`t find any reversible causes for the heart rate acceleration, we opted for rate control with atrioventricular node ablation. To counteract the risk of pacing-induced cardiomyopathy in this patient who would become totally pacemaker-dependent, we successfully performed left bundle branch area pacing. Because the patient`s ICD had a DF-1 connection and the battery had a long life remaining, we connected the physiological pacing lead to the IS-1 sense-pace port of the ICD. The 6-month follow-up showed an improvement in left ventricular function with no more inappropriate shocks.ConclusionsLeft bundle branch area pacing and atrioventricular node ablation in patients with an implantable single-chamber DF-1 defibrillator and fast-conducting permanent atrial fibrillation is a cost-efficient and very effective method to prevent and treat inappropriate shocks, avoiding the use of an additional dual-chamber or CRT-D device.

Reshaping Prognosis: Atrial fibrillation ablation in a case of severe tachycardiomyopathy in a young patient

Abstract Tachycardiomyopathy, characterized by ventricular systolic dysfunction resulting from persistent tachycardia, poses a significant challenge in cardiovascular disease management. This article presents the case of a 31-year-old male patient with dilated cardiomyopathy and recurrent persistent atrial fibrillation, admitted due to heart failure decompensation. Ischemic and inflammatory etiologies for heart failure were ruled out in prior assessments. Despite multiple antiarrhythmic drugs and attempted electrical cardioversion, sinus rhythm was not maintained. Echocardiography confirmed a decline in the already reduced ejection fraction. Atrial fibrillation cryoablation was performed, and procedural specifics are detailed. Subsequent follow-up visits revealed a noteworthy improvement in exercise tolerance and ventricular function. This case underscores the importance of considering tachycardiomyopathy in the differential diagnosis of new-onset or worsening heart failure and highlights the potential for symptom resolution and ventricular function recovery with atrial fibrillation ablation.

Comparing the impact of left bundle branch area pacing and traditional left ventricular pacing on right heart function following dual-chamber pacemaker implantation

Objective: To compare the effects of left bundle branch area pacing (LBBaP) versus traditional right ventricular pacing (RVP) on left ventricular function in patients after dual-chamber pacemaker implantation. Methods: A retrospective cohort study was conducted on patients who underwent dual-chamber pacemaker implantation from March 2017 to April 2021 in Beijing Anzhen Hospital. The patients were divided into the LBBaP group and RVP group based on the placement of the ventricular lead. Follow-up was conducted until March 2022, comparing baseline and follow-up echocardiographic parameters, pacing parameters, and the incidence and timing of complications between the two groups. The complications included ventricular electrode perforation, dislocation, pericardial effusion, tricuspid valve perforation, etc. Results: A total of 163 patients aged (68.3±13.5) years were included, including 82 (50.3%) men, with 80 patients in the LBBaP group and 83 in the RVP group. Baseline left ventricular end-diastolic diameter ((50.49±4.95) mm vs. (47.43±8.15) mm, P=0.01) and left atrium (LA) ((33.14±5.94) mm vs. (30.18±3.92) mm, P=0.001) in the LBBaP group were significantly higher than those in the RVP group. Follow-up LA diameter ((37.10±6.70) mm vs. (40.10±8.90) mm, P=0.016) showed a statistically significant difference in the LBBaP group compared to the RVP group. There was no statistically significant difference between the two groups in baseline QRS duration(P=0.490). Postoperative QRS duration in the LBBaP group was significantly lower ((110.69±24.01) ms vs. (139.65±29.85) ms, P<0.010). Intraoperative threshold in the LBBaP group was significantly higher ((0.83±0.32) V/0.48 ms vs. (0.71±0.23) V/0.48 ms, P=0.004), while impedance was lower ((754.53±205.59) Ω vs. (905.41±302.75) Ω, P<0.01). Comparing with the RVP group, postoperative ventricular pacing ratio (VP) ((87.39±20.92) % vs. (79.49±25.76) %, P=0.034), threshold ((0.90±0.38) V/0.48 ms vs. (0.69±0.27) V/0.48 ms, P<0.01) in the LBBaP group were higher, and impedance ((507.45±77.37) Ω vs. (620.52±197.29) Ω, P<0.01) in the LBBaP group was lower. Postoperative follow-up period was 5 to 51 months, with a median follow-up time of 17 months. No statistically significant difference in overall complications between the LBBaP and RVP groups was found (13.8% (11/80) vs. 7.2% (6/83), P>0.05). The median time to occurrence of complications after surgery was significantly earlier in the LBBaP group (29.74 (95%CI 27.21-32.26) months vs. 46.17 (95%CI 42.48-49.86) months, P=0.030). Conclusion: LBBaP demonstrates more stable pacing parameters, substantial improvement in clinical left ventricular function, with a relatively higher threshold compared to traditional RVP, and complications occurs relatively early.

The siRNA-mediated knockdown of AP-1 restores the function of the pulmonary artery and the right ventricle by reducing perivascular and interstitial fibrosis and key molecular players in cardiopulmonary disease.

Pulmonary hypertension (PH) is a complex multifactorial vascular pathology characterized by an increased pulmonary arterial pressure, vasoconstriction, remodelling of the pulmonary vasculature, thrombosis in situ and inflammation associated with right-side heart failure. Herein, we explored the potential beneficial effects of treatment with siRNA AP-1 on pulmonary arterial hypertension (PAH), right ventricular dysfunction along with perivascular and interstitial fibrosis in pulmonary artery-PA, right ventricle-RV and lung in an experimental animal model of monocrotaline (MCT)-induced PAH. Golden Syrian hamsters were divided into: (1) C group-healthy animals taken as control; (2) MCT group obtained by a single subcutaneous injection of 60mg/kg MCT at the beginning of the experiment; (3) MCT-siRNA AP-1 group received a one-time subcutaneous dose of MCT and subcutaneous injections containing 100nM siRNA AP-1, every two weeks. All animal groups received water and standard chow ad libitum for 12weeks. In comparison with the MCT group, siRNA AP-1 treatment had significant beneficial effects on investigated tissues contributing to: (1) a reduction in TGF-β1/ET-1/IL-1β/TNF-α plasma concentrations; (2) a reduced level of cytosolic ROS production in PA, RV and lung and notable improvements regarding the ultrastructure of these tissues; a decrease of inflammatory and fibrotic marker expressions in PA (COL1A/Fibronectin/Vimentin/α-SMA/CTGF/Calponin/MMP-9), RV and lung (COL1A/CTGF/Fibronectin/α-SMA/F-actin/OB-cadherin) and an increase of endothelial marker expressions (CD31/VE-cadherin) in PA; (4) structural and functional recoveries of the PA [reduced Vel, restored vascular reactivity (NA contraction, ACh relaxation)] and RV (enlarged internal cavity diameter in diastole, increased TAPSE and PRVOFs) associated with a decrease in systolic and diastolic blood pressure, and heart rate; (5) a reduced protein expression profile of AP-1S3/ pFAK/FAK/pERK/ERK and a significant decrease in the expression levels of miRNA-145, miRNA-210, miRNA-21, and miRNA-214 along with an increase of miRNA-124 and miRNA-204. The siRNA AP-1-based therapy led to an improvement of pulmonary arterial and right ventricular function accompanied by a regression of perivascular and interstitial fibrosis in PA, RV and lung and a down-regulation of key inflammatory and fibrotic markers in MCT-treated hamsters.

Conduction System Pacing in Pediatrics and Congenital Heart Disease: A Case Report and Literature Review.

Conduction system pacing involving either His bundle pacing (HBP) or left bundle branch pacing (LBBP) is a modality that has been introduced as a safe and effective alternative to right ventricular (RV) pacing to help prevent pacemaker-associated cardiomyopathy. While HBP has been employed in the pediatric and congenital populations, several small studies have shown LBBP to be safe and effective in the pediatric population. We present a patient with congenital atrioventricular block and postoperative ventricular septal defect repair cardiomyopathy with subsequent left ventricular function improvement following a transition from an RV epicardial pacemaker system to an LBBP system. This case report serves as a foundation for a review of the current state of LBBP in pediatrics and congenital heart disease.

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

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

Colchicine ameliorates myocardial injury induced by coronary microembolization through suppressing pyroptosis via the AMPK/SIRT1/NLRP3 signaling pathway

BackgroundCoronary microembolization(CME)is a common complication in acute coronary syndrome and percutaneous coronary intervention, which is closely related to poor prognosis. Pyroptosis, as an inflammatory programmed cell death, has been found to be associated with CME-induced myocardial injury. Colchicine (COL) has potential benefits in coronary artery disease due to its anti-inflammatory effect. However, the role of colchicine in pyroptosis-related CME-induced cardiomyocyte injury is unclear. This study was carried out to explore the effects and mechanisms of colchicine on myocardial pyroptosis induced by CME.MethodsThe CME animal model was constructed by injecting microspheres into the left ventricle with Sprague-Dawley rats, and colchicine (0.3 mg/kg) pretreatment seven days before and on the day of modeling or compound C(CC)co-treatment was given half an hour before modeling. The study was divided into 4 groups: Sham group, CME group, CME + COL group, and CME + COL + CC group (10 rats for each group). Cardiac function, serum myocardial injury markers, myocardial histopathology, and pyroptosis-related indicators were used to evaluate the effects of colchicine.ResultsColchicine pretreatment improved cardiac dysfunction and reduced myocardial injury induced by CME. The main manifestations were the improvement of left ventricular systolic function, the decrease of microinfarction area, and the decrease of mRNA and protein indexes related to pyroptosis. Mechanistically, colchicine increased the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK), promoted the expression of silent information regulation T1 (SIRT1), and inhibited the expression of NOD-like receptor pyrin containing 3 (NLRP3) to reduce myocardial pyroptosis. However, after CC co-treatment with COL, the effect of colchicine was partially reversed.ConclusionColchicine improves CME-induced cardiac dysfunction and myocardial injury by inhibiting cardiomyocyte pyroptosis through the AMPK/SIRT1/NLRP3 signaling pathway.

Peripartum Cardiomyopathy: A Case Report

Background: Peripartum cardiomyopathy (PPCM) is a type of dilated cardiomyopathy of unknown origin. Predisposing factors for PPCM are multiparity, family history, ethnicity, smoking, diabetes, hypertension, preeclampsia, malnutrition, and advanced age in pregnant women or teenage pregnancy.&#x0D; Case presentation: A 29-year-old female patient was treated in the internal medicine department of Dr. M. Djamil General Hospital Padang on March 18th, 2023, with the main complaint of shortness of breath. On physical examination, signs of congestion were found. ECG shows sinus tachycardia, QT prolongation, and T inversion in V3-V6, II, III, and aVF. The patient is established with peripartum cardiomyopathy, community-acquired pneumonia, nonsevere low-risk MDR, hypochromic microcytic mild anemia et causa chronic disease, high-risk VTE, h hypokalemia et causa diuretic.&#x0D; Conclusion: Education regarding recurrent recurrence of PPCM in subsequent pregnancies is 30-50%. The prognosis depends on the recovery of left ventricular function; 30% of patients can return to baseline ventricular function within 6 months, and 50% of patients have an improvement in symptoms and ventricular function. Contraception is recommended that does not pose a risk of thromboembolism, such as a uterine device (IUD) and subcutaneous progesterone.

Myocardial infarct size for predicting improvements in cardiac function in patients with ischemic cardiomyopathy following coronary artery bypass grafting.

This study used late gadolinium enhancement-cardiac magnetic resonance (LGE-CMR) to assess myocardial infarct size, with the data being employed to predict whether patients with ischemic cardiomyopathy (ICM) would experience improvements in left ventricular function at 6 months following coronary artery bypass grafting (CABG). The data of patients with ICM with left ventricular ejection fraction (LVEF) ≤40% who underwent CABG were retrospectively analyzed. All patients underwent preoperative LGE-CMR imaging. Echocardiography results from 6 months post-CABG were used to assess improvements in LVEF, with improvement being defined as ΔLVEF ≥5%. The value of myocardial infarction segments and infarct size as predictors of improved cardiac function following CABG was analyzed. Of the included patients, 66.7% (52/78) exhibited improved cardiac function at 6 months post-CABG. LGE-CMR imaging data revealed that compared to improved group, the improved group had significantly more myocardial infarct segments [improved group: median 1.0, interquartile range (IQR) 0-3; nonimproved group: median 4.0, IQR 3.0-6.0; P<0.001] and significantly greater myocardial infarct size (improved group: 22.4%±8.2%; nonimproved group: 34.7%±5.9%; P<0.001). The area under the receive operating characteristic curve values for myocardial infarct size in predicting cardiac function improvement were significantly higher than those of myocardial infarct segments (0.88 vs. 0.81; P=0.041). The respective sensitivity and specificity values for using a myocardial infarct size cutoff of 26.4% in differentiating between these 2 patient groups were 92.3% and 71.2%, respectively. According to logistic regression analysis, myocardial infarct size was an independent predictor of nonimprovement in cardiac function [odds ratio (OR) =1.244; 95% confidence interval (CI): 1.114-1.389; P<0.001]. A median 1.6-year follow-up interval (range, 0.5-4.1 years) revealed that the incidences of major adverse cerebrovascular events and cardiovascular events were significantly higher in the nonimproved group (5.8% vs. 26.9%; P<0.001), with these individuals having a higher New York Heart Association grading than patients with improved cardiac function (P=0.019). Myocardial infarct size can be measured to reliably predict improvements in cardiac function in patients with ICM following CABG. These results can guide clinicians in their efforts to identify those patients most likely to achieve positive outcomes following CABG.