Percutaneous Intervention of LVAD Outflow Graft Obstruction and Thrombosis.

Left ventricular assist devices serve as a salvage therapy for patients with advanced heart failure. Complications such as thrombosis and obstruction can lead to acute device malfunction, posing significant clinical risks. A multidisciplinary approach is crucial for management. Few cases in the literature have demonstrated the safety and efficacy of percutaneous intervention, which holds significant value due to its less invasive nature and minimal risk of morbidity, especially in high-risk surgical patients.

A Murine Model of Hyperlipidemia-Induced Heart Failure with Preserved Ejection Fraction.

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) driven by lipotoxicity is incompletely understood. Given the urgent need for animal models that accurately mimic cardio-metabolic HFpEF, a hyperlipidemia-induced murine model was developed by reverse engineering phenotypes seen in HFpEF patients. This model aimed to investigate HFpEF, focusing on the interplay between lipotoxicity and metabolic syndrome. Hyperlipidemia was induced in wild-type (WT) mice on a 129J strain background through bi-weekly intraperitoneal injections of poloxamer-407 (P-407), a block co-polymer that blocks lipoprotein lipase, combined with a single intravenous injection of adeno-associated virus 9-cardiac troponin T-low-density lipoprotein receptor (AAV9-cTnT-LDLR). Extensive assessments were conducted between 4 and 8 weeks post-treatment, including echocardiography, blood pressure recording, whole-body plethysmography, echocardiography (ECG) telemetry, activity wheel monitoring (AWM), and biochemical and histological analyses. The LDLR/P-407 mice exhibited distinctive features at four weeks, including diastolic dysfunction, preserved ejection fraction, and increased left ventricular wall thickness. Notably, blood pressure and renal function remained within normal ranges. Additionally, ECG and AWM revealed heart blocks and reduced activity, respectively. Diastolic function deteriorated at eight weeks, accompanied by a significant decline in respiratory rates. Further investigation into the double treatment model revealed elevated fibrosis, wet/dry lung ratios, and heart weight/body weight ratios. The LDLR/P-407 mice exhibited xanthelasmas, ascites, and cardiac ischemia. Interestingly, sudden deaths occurred between 6 and 12 weeks post-treatment. The murine HFpEF model offers a valuable and promising experimental resource for elucidating the intricacies of metabolic syndrome contributing to diastolic dysfunction within the context of lipotoxicity-mediated HFpEF.

Associations between cardiovascular diseases and cancer mortality: insights from a retrospective cohort analysis of NHANES data.

BACKGROUND: This study explored the association of cardiovascular disease (CVD) with cancer mortality risk in individuals with or without a history of cancer, to better understand the interplay between CVD and cancer outcomes. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018, a retrospective cohort analysis was conducted. This analysis accounted for the survey's complex design to ensure national representativeness. The association of CVD with cancer mortality was assessed through multivariable Cox proportional hazards models. RESULTS: The present study included 59,653 participants, of whom 54,095 did not have cancer and 5558 had a history of cancer. In individuals without cancer, heart failure (HF) was associated with an increased risk of mortality from cancer (HR, 1.36; 95% CI, 1.09-1.69; P = 0.005). In participants with cancer, HF correlated with a higher risk of mortality from cancer (HR, 1.76; 95% CI, 1.32-2.34; P < 0.001). Diabetes (DM), hypertension (HBP) and coronary heart disease (CHD) were not significantly associated with an increased risk of mortality from cancer. Significant differences were observed in the interaction between cancer and CHD (HR, 0.68; 95% CI, 0.53-0.87; P = 0.002). For cancer and HBP, a similar trend was noted (HR, 0.75; 95% CI, 0.62-0.91; P = 0.003). No significant differences were found in interactions between HF, DM and cancer. CONCLUSIONS: HF was associated with an increased risk of mortality from cancer, regardless of cancer history, while HBP, CHD and DM showed no significant association. These findings underscore the importance of understanding the mechanisms behind the increased risk of cancer mortality following HF.

Plastic Surgery Involvement With Surgical Management of Infected Ventricular Assist Devices Decreased Lifetime Return to Operating Room and 90-Day Infectious Complications.

BACKGROUND: The use of left ventricular assist devices (LVADs) for patients with end-stage cardiac failure awaiting heart transplantation has become increasingly common. However, ventricular assist device-related infections remain a major problem complicating their long-term use. Retrospective review has previously shown a decrease in lifetime return to operating room (RTOR) with no change in 90-day complications when a muscle or omental flap is used for coverage after washout for infection. We wished to determine if early plastic surgery intervention led to a decreased length of stay for these patients. METHODS: Patients with LVAD readmitted for LVAD infection at a single institution from 2008 to 2021 were identified using a preexisting database. Patients were followed retrospectively for an average of 3.2 years. Patient demographics, preoperative diagnosis/disease state, type of ventricular assist device inserted, postoperative day of ventricular assist device infection onset, definitive device coverage, timing of coverage procedure after the initial washout for infection, type of flap used for coverage, 90-day complications after definitive coverage, and lifetime return to operating room for infection were reviewed. Comparison analysis with χ2 and analysis of variance testing was used to analyze outcomes. RESULTS: Of 568 patients admitted with an LVAD infection, 104 underwent operative debridement and closure by plastic and reconstructive surgery (PRS) or cardiothoracic surgery (CTS). Fifty-three underwent PRS closure, and 51 underwent CTS closure. There was an increased incidence of diabetes among the PRS group (P < 0.001); otherwise, there was no difference in baseline characteristics. There was increased RTOR over a lifetime with CTS closure compared with PRS (P = 0.03) and increased 90-day risk of infection (P = 0.007). Patients with PRS closure had an increased risk of postoperative hematoma (P = 046). Plastic and reconstructive surgery was typically consulted on hospital day 10. Both PRS and CTS closure patients were discharged on postoperative day 7, on average (P = 0.542). CONCLUSIONS: Plastic surgery involvement with surgical decision making and closure of infected LVAD devices has a decrease in lifetime RTOR and decreased 90-day complications related to infections. There may be a benefit to earlier PRS consultation for coverage assessment.

[Acute heart failure in a neonate]. / æ–°ç”Ÿå„¿æ€¥æ€§å¿ƒåŠŸèƒ½ä¸å ¨1例.

The male patient, one day old, was admitted to the hospital due to hypoglycemia accompanied by apnea appearing six hours after birth. The patient had transient hypoglycemia early after birth, and acute heart failure suddenly occurred on the eighth day after birth. Laboratory tests showed significantly reduced levels of adrenocorticotropic hormone and cortisol, and pituitary magnetic resonance imaging was normal. Genetic testing results showed that the patient had probably pathogenic compound heterozygous mutations of the TBX19 gene (c.917-2A>G+c.608C>T), inherited respectively from the parents. The patient was conclusively diagnosed with congenital isolated adrenocorticotropic hormone deficiency caused by mutation of the TBX19 gene. Upon initiating hydrocortisone replacement therapy, cardiac function rapidly returned to normal. After being discharged, the patient continued with the hydrocortisone replacement therapy. By the 18-month follow-up, the patient was growing and developing well. In neonates, unexplained acute heart failure requires caution for possible endocrine hereditary metabolic diseases, and timely cortisol testing and genetic testing should be conducted.

Systemic immune-inflammation index as a novel predictor of major adverse cardiovascular events in patients undergoing percutaneous coronary intervention: a meta-analysis of cohort studies.

BACKGROUND: The Systemic Immune-Inflammation Index (SII), a novel marker of inflammation based on neutrophil, platelet, and lymphocyte counts, has demonstrated potential prognostic value in patients undergoing percutaneous coronary intervention (PCI). Our aim was to assess the correlation between the SII and major adverse cardiovascular events following percutaneous coronary intervention. METHODS: We searched PubMed, Web of Science, Embase, and The Cochrane Library from inception to November 20, 2023, for cohort studies investigating the association between SII and the occurrence of MACEs after PCI. Statistical analysis was performed using Revman 5.3, with risk ratios (RRs) and 95% confidence intervals (CIs) as relevant parameters. RESULTS: In our analysis, we incorporated a total of 8 studies involving 11,117 participants. Our findings revealed that a high SII is independently linked to a increased risk of MACEs in PCI patients (RR: 2.08,95%CI: 1.87-2.32, I2 = 42%, p < 0.00001). Additionally, we demonstrated the prognostic value of SII in all-cause mortality, heart failure, and non-fatal myocardial infarction. CONCLUSIONS: Elevated SII may serve as a potential predictor for subsequent occurrence of MACEs in patients undergoing PCI. TRIAL REGISTRATION: Our protocol was registered in PROSPERO (registration number: CRD42024499676).

[Morphofunctional Analysis of the Role of Epicardial Adipose Tissue in the Formation of the Obesity Paradox in Chronic Heart Failure].

Based on the available modern medical literature, the article summarizes data on the morpho-functional significance of epicardial adipose tissue (EAT) in health and heart failure, analyzes the likelihood and reliability of the formation of the obesity paradox, and also discusses its possible morpho-functional mechanisms. The authors reviewed and analyzed the consequences of the obesity paradox in the aspect of the normal EAT phenotype protectivity. The review proposed ways of further research in this direction aimed at a deep anatomical and physiological analysis and at determining the morpho-functional role of EAT in the adaptive mechanisms of myocardial trophic provision, which may be an important part of the pathogenetic connection between obesity and CHF and, therefore, can improve outcomes in such patients.

Prediction of Mortality and Heart Failure Hospitalization After Transcatheter Tricuspid Valve Interventions: Validation of TRISCORE.

BACKGROUND: Data on the prognostic role of the TRI-SCORE in patients undergoing transcatheter tricuspid valve intervention (TTVI) are limited. OBJECTIVES: The aim of this study was to evaluate the performance of the TRI-SCORE in predicting outcomes of patients undergoing TTVI. METHODS: TriValve (Transcatheter Tricuspid Valve Therapies) is a large multicenter multinational registry including patients undergoing TTVI. The TRI-SCORE is a risk model recently proposed to predict in-hospital mortality after tricuspid valve surgery. The TriValve population was stratified based on the TRI-SCORE tertiles. The outcomes of interest were all-cause death and all-cause death or heart failure hospitalization. Procedural complications and changes in NYHA functional class were also reported. RESULTS: Among the 634 patients included, 223 patients (35.2%) had a TRI-SCORE between 0 and 5, 221 (34.8%) had 6 or 7, and 190 (30%) had ≥8 points. Postprocedural blood transfusion, acute kidney injury, new atrial fibrillation, and in-hospital mortality were more frequent in the highest TRI-SCORE tertile. Postprocedure length of stay increased with a TRI-SCORE increase. A TRI-SCORE ≥8 was associated with an increased risk of 30-day all-cause mortality and all-cause mortality and the composite endpoint assessed at a median follow-up of 186 days (OR: 3.00; 95% CI: 1.38-6.55; HR: 2.17; 95% CI: 1.78-4.13; HR: 2.08, 95% CI: 1.57-2.74, respectively) even after adjustment for procedural success and EuroSCORE II or Society of Thoracic Surgeons Predicted Risk of Mortality. The NYHA functional class improved across all TRI-SCORE values. CONCLUSIONS: In the TriValve registry, the TRI-SCORE has a suboptimal performance in predicting clinical outcomes. However, a TRISCORE ≥8 is associated with an increased risk of clinical events and a lack of prognostic benefit after successful TTVI.

Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.

BACKGROUND: Obesity and type 2 diabetes are prevalent in patients with heart failure with preserved ejection fraction and are characterized by a high symptom burden. No approved therapies specifically target obesity-related heart failure with preserved ejection fraction in persons with type 2 diabetes. METHODS: We randomly assigned patients who had heart failure with preserved ejection fraction, a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more, and type 2 diabetes to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: A total of 616 participants underwent randomization. The mean change in the KCCQ-CSS was 13.7 points with semaglutide and 6.4 points with placebo (estimated difference, 7.3 points; 95% confidence interval [CI], 4.1 to 10.4; P<0.001), and the mean percentage change in body weight was -9.8% with semaglutide and -3.4% with placebo (estimated difference, -6.4 percentage points; 95% CI, -7.6 to -5.2; P<0.001). The results for the confirmatory secondary end points favored semaglutide over placebo (estimated between-group difference in change in 6-minute walk distance, 14.3 m [95% CI, 3.7 to 24.9; P = 0.008]; win ratio for hierarchical composite end point, 1.58 [95% CI, 1.29 to 1.94; P<0.001]; and estimated treatment ratio for change in CRP level, 0.67 [95% CI, 0.55 to 0.80; P<0.001]). Serious adverse events were reported in 55 participants (17.7%) in the semaglutide group and 88 (28.8%) in the placebo group. CONCLUSIONS: Among patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, semaglutide led to larger reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo at 1 year. (Funded by Novo Nordisk; STEP-HFpEF DM ClinicalTrials.gov number, NCT04916470.).

Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction.

BACKGROUND: Most trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists. METHODS: In a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction. RESULTS: From September 2017 through May 2023, a total of 5020 patients were enrolled (95.4% of whom were from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7). A primary end-point event occurred in 199 of 2508 patients (7.9%) in the beta-blocker group and in 208 of 2512 patients (8.3%) in the no-beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; P = 0.64). Beta-blocker treatment did not appear to lead to a lower cumulative incidence of the secondary end points (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no-beta-blocker group; death from cardiovascular causes, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%). With regard to safety end points, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker occurred in 3.4% of the patients in the beta-blocker group and in 3.2% of those in the no-beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease in 0.6% and 0.6%, respectively; and hospitalization for stroke in 1.4% and 1.8%. CONCLUSIONS: Among patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509.).

Toward a Universal Definition of Etiologies in Heart Failure: Categorizing Causes and Advancing Registry Science.

Heart failure (HF) is a well-described final common pathway for a broad range of diseases however substantial confusion exists regarding how to describe, study, and track these underlying etiologic conditions. We describe (1) the overlap in HF etiologies, comorbidities, and case definitions as currently used in HF registries led or managed by members of the global HF roundtable; (2) strategies to improve the quality of evidence on etiologies and modifiable risk factors of HF in registries; and (3) opportunities to use clinical HF registries as a platform for public health surveillance, implementation research, and randomized registry trials to reduce the global burden of noncommunicable diseases. Investment and collaboration among countries to improve the quality of evidence in global HF registries could contribute to achieving global health targets to reduce noncommunicable diseases and overall improvements in population health.

Cardiovascular outcomes following hospitalisation for exacerbation of bronchiectasis: a territory-wide study.

BACKGROUND: Although bronchiectasis is reported to be associated with cardiovascular disease, evidence for an association with cardiovascular events (CVEs) is lacking. METHODS: A territory-wide retrospective cohort study was conducted in Hong Kong involving all patients who had bronchiectasis diagnosed in public hospitals and clinics between 1 January 1993 and 31 December 2017 were included. Patients were allocated to be exacerbator or non-exacerbator group based on hospitalzied bronchiecsis history and CVEs over the next 5 years determined. Propensity score matching was used to balance baseline characteristics. RESULTS: 10 714 bronchiectasis patients (mean age 69.6±14.4 years, 38.9% men), including 1230 in exacerbator group and 9484 in non-exacerbator group, were analysed. At 5 years, 113 (9.2%) subjects in the exacerbator group and 87 (7.1%) in the non-exacerbator group developed composite CVEs. After adjustment for age, sex, smoking and risk factors for cardiovascular disease, bronchiectasis exacerbation was associated with increased risks for acute myocardial infarction (AMI), congestive heart failure (CHF) and CVE compared with those in the non-exacerbator group with adjusted HR of 1.602 (95% CI 1.006-2.552, p value=0.047), 1.371 (95% CI 1.016-1.851, p value=0.039) and 1.238 (95% CI 1.001-1.532, p=0.049) in the whole cohort. Findings were similar for the propensity score-matched cohort for AMI and CVE. CONCLUSION: Patients who were hospitalised for exacerbation of bronchiectasis were at significantly increased risk of AMI, CHF and CVE over a 5-year follow-up period.

Atrial fibrillation ablation compared to pacemaker therapy in patients with tachycardia-bradycardia syndrome: A systematic review and updated meta-analysis.

BACKGROUND: Tachycardia-bradycardia syndrome (TBS) is a subtype of sick sinus syndrome characterized by prolonged sinus pause (≥3 s) following termination of tachyarrhythmias, primarily atrial fibrillation (AF). There is controversy regarding whether the long-term prognosis of AF ablation is superior to pacemaker implantation. This study aimed to compare the effects of AF ablation and pacemaker therapy in patients with TBS. METHODS: We conducted a comprehensive search of electronic databases, including PubMed, Cochrane, EmBase, Web of Science, and Chinese BioMedical, up until December 1, 2023. We included studies that reported the effects of AF ablation vs pacemaker therapy in patients with TBS. From this search, we identified 5 studies comprising 843 participants with TBS who underwent catheter AF ablation or pacemaker therapy. RESULTS: Our meta-analysis revealed that AF ablation and pacemaker therapy had similar effects on cardiovascular death (odds ratio [OR] = 0.62 and 95% confidence interval [CI]: 0.14-2.65), procedural complications (OR = 1.53 and 95% CI: 0.67-3.48), and cardiovascular rehospitalization (OR = 0.57 and 95% CI: 0.26-1.22). However, AF ablation provided greater benefits than pacemaker therapy in terms of all-cause mortality (OR = 0.37 and 95% CI: 0.17-0.82), thromboembolism (OR = 0.25 and 95% CI: 0.12-0.49), stroke (OR = 0.28 and 95% CI: 0.13-0.57), heart failure (OR = 0.27 and 95% CI: 0.13-0.56), freedom from AF (OR = 23.32 and 95% CI: 7.46-72.92), and prevention of progression to persistent AF (OR = 0.12 and 95% CI: 0.06-0.24). Furthermore, AF ablation resulted in a reduced need for antiarrhythmic agents (OR = 0.21 and 95% CI: 0.08-0.59). CONCLUSION: AF ablation can effectively reduce the risk of all-cause mortality, thromboembolism, stroke, heart failure, and progression to persistent AF in patients with TBS. Additionally, it may eliminate the need for further pacemaker therapy in most cases after ablation. Therefore, AF ablation is considered superior to pacemaker therapy in the management of patients with TBS.

Assessment of new-onset heart failure prediction in a diabetic population using left ventricular global strain: a prospective cohort study based on UK Biobank.

Background: Impaired glucose utilization influences myocardial contractile function. However, the prognostic importance of left ventricular global radial strain (LV-GRS), left ventricular global circumferential strain (LV-GCS), and left ventricular global longitudinal strain (LV-GLS) in predicting new-onset heart failure (HF) in a population with diabetes is unclear. Methods: The study design is prospective cohort from the UK Biobank. Totally 37,899 participants had a complete data of cardiac magnetic resonance (CMR), of which 940 patients with diabetes were included, and all the participants completed follow-up. LV-GRS, LV-GCS, and LV-GLS were measured by completely automated CMR with tissue tagging. Cox proportional hazards regression analysis and C-index was performed to evaluate the association between the strain parameters and the new-onset HF in patients suffering from diabetes. Results: The average age of the 940 participants was 57.67 ± 6.97 years, with males comprising 66.4% of the overall population. With an average follow-up period of 166.82 ± 15.26 months, 35 (3.72%) patients reached the endpoint (emergence of new-onset HF). Significant associations were found for the three strain parameters and the new-onset HF (LV-GRS-hazard ratio [HR]: 0.946, 95% CI: 0.916-0.976; LV-GCS-HR: 1.162, 95% CI: 1.086-1.244; LV-GCS-HR: 1.181, 95% CI: 1.082-1.289). LV-GRS, LV-GCS, and LV-GLS were closely related to the related indicators to HF, and showed a high relationship to new-onset HF in individuals with diabetes at 5 and 10 years: LV-GRS: 0.75 (95% CI, 0.41-0.94) and 0.76 (95% CI, 0.44-0.98), respectively; LV-GCS: 0.80 (95% CI, 0.50-0.96) and 0.75 (95% CI, 0.41-0.98), respectively; LV-GLS: 0.72 (95% CI, 0.40-0.93) and 0.76 (95% CI, 0.48-0.97), respectively. In addition, age, sex, body mass index (BMI), and presence of hypertension or coronary artery disease (CAD) made no impacts on the association between the global strain parameters and the incidence of HF. Conclusion: LV-GRS, LV-GCS, and LV-GLS is significantly related to new-onset HF in patients with diabetes at 5 and 10 years.

Right ventricular myocardial edema leading to severe heart failure after open heart surgery - possible effect of high-dose corticosteroid therapy.

BACKGROUND: Cardiopulmonary bypass induces a systemic inflammatory response and alterations in fluid homeostasis, resulting in generalized tissue edema. Additionally, ischemia-reperfusion injury following cardioplegic arrest presumably prompts organ-specific myocardial edema. CASE PRESENTATION: The case report presents a 75-year-old Caucasian male diagnosed with aortic dissection, Stanford type A, who underwent complicated open-heart surgery. Postoperatively, the patient developed excessive myocardial edema, particularly affecting the right ventricle myocardium to an extent where the right ventricle surpassed the sternal rim, making it impossible to close the sternum. Ischemia was ruled out by performing coronary angiography, demonstrating well-calibrated coronary arteries. Transoesophageal echocardiography showed a restrictive right ventricle with free-wall thickness of 30 mm, severely reduced right ventricle systolic function and a volume-depleted left ventricle consistent with right ventricular heart failure due to right ventricular edema. The patient presented with unstable haemodynamics despite use of inotropes and continuation of open sternotomy. In an attempt to reduce myocardial edema, the patient was started on corticosteroid treatment despite of ongoing mediastinitis. Corticosteroid treatment reduced myocardial edema and enabled the closure of sternum on the 44th postoperative day. CONCLUSIONS: The case report addresses the clinical relevance of corticosteroid treatment in selective cases of intractable haemodynamically significant postoperative myocardial edema.

A division-of-labor mode contributes to the cardioprotective potential of mesenchymal stem/stromal cells in heart failure post myocardial infarction.

Background: Treatment of heart failure post myocardial infarction (post-MI HF) with mesenchymal stem/stromal cells (MSCs) holds great promise. Nevertheless, 2-dimensional (2D) GMP-grade MSCs from different labs and donor sources have different therapeutic efficacy and still in a low yield. Therefore, it is crucial to increase the production and find novel ways to assess the therapeutic efficacy of MSCs. Materials and methods: hUC-MSCs were cultured in 3-dimensional (3D) expansion system for obtaining enough cells for clinical use, named as 3D MSCs. A post-MI HF mouse model was employed to conduct in vivo and in vitro experiments. Single-cell and bulk RNA-seq analyses were performed on 3D MSCs. A total of 125 combination algorithms were leveraged to screen for core ligand genes. Shinyapp and shinycell workflows were used for deploying web-server. Result: 3D GMP-grade MSCs can significantly and stably reduce the extent of post-MI HF. To understand the stable potential cardioprotective mechanism, scRNA-seq revealed the heterogeneity and division-of-labor mode of 3D MSCs at the cellular level. Specifically, scissor phenotypic analysis identified a reported wound-healing CD142+ MSCs subpopulation that is also associated with cardiac protection ability and CD142- MSCs that is in proliferative state, contributing to the cardioprotective function and self-renewal, respectively. Differential expression analysis was conducted on CD142+ MSCs and CD142- MSCs and the differentially expressed ligand-related model was achieved by employing 125 combination algorithms. The present study developed a machine learning predictive model based on 13 ligands. Further analysis using CellChat demonstrated that CD142+ MSCs have a stronger secretion capacity compared to CD142- MSCs and Flow cytometry sorting of the CD142+ MSCs and qRT-PCR validation confirmed the significant upregulation of these 13 ligand factors in CD142+ MSCs. Conclusion: Clinical GMP-grade 3D MSCs could serve as a stable cardioprotective cell product. Using scissor analysis on scRNA-seq data, we have clarified the potential functional and proliferative subpopulation, which cooperatively contributed to self-renewal and functional maintenance for 3D MSCs, named as "division of labor" mode of MSCs. Moreover, a ligand model was robustly developed for predicting the secretory efficacy of MSCs. A user-friendly web-server and a predictive model were constructed and available (https://wangxc.shinyapps.io/3D_MSCs/).

Characterization of Non-Ischemic Dilated Cardiomyopathy in a Native Tanzanian Cohort: MOYO Study.

Background: Non-ischemic dilated cardiomyopathy (NIDCM) is a common cause of heart failure with progressive tendency. The disease occurs in one in every 2,500 individuals in the developed world, with high morbidity and mortality. However, detailed data on the role of NIDCM in heart failure in Tanzania is lacking. Aim: To characterize NIDCM in a Tanzanian cohort with respect to demographics, clinical profile, imaging findings and management. Methods: Characterization of non-ischemic dilated cardioMyOpathY in a native Tanzanian cOhort (MOYO) is a prospective cohort study of NIDCM patients seen at the Jakaya Kikwete Cardiac Institute. Patients aged ≥18 years with a clinical diagnosis of heart failure, an ejection fraction of ≤45% on echocardiography and no evidence of ischemia were enrolled. Clinical data, echocardiography, electrocardiography (ECG), coronary angiography and stress ECG information were collected from February 2020 to March 2022. Results: Of 402 patients, n = 220 (54.7%) were males with a median (IQR) age of 55.0 (41.0, 66.0) years. Causes of NIDCM were presumably hypertensive n = 218 (54.2%), idiopathic n = 116 (28.9%), PPCM n = 45 (11.2%), alcoholic n = 10 (2.5%) and other causes n = 13 (3.2%). The most common presenting symptoms were dyspnea n = 342 (85.1%), with the majority of patients presenting with New York Heart Association (NYHA) Class III n = 195 (48.5%). The mean (SD) left ventricular ejection fraction (LVEF) was 29.4% (±7.7), and severe systolic dysfunction (LVEF <30%) was common n = 208 (51.7%). Compared with other forms of DCM, idiopathic DCM patients were significantly younger, had more advanced NYHA class (p < 0.001) and presented more often with left bundle branch block on ECG (p = 0.0042). There was suboptimal use of novel guidelines recommended medications ARNI n = 10 (2.5%) and SGLT2 2-inhibitors n = 2 (0.5%). Conclusions: In our Tanzanian cohort, the majority of patients with NIDCM have an identified underlying cause, and they present at late stages of the disease. Patients with idiopathic DCM are younger with more severe disease compared to other forms of NIDCM.

Electro-anatomically-guided endomyocardial biopsy in a patient with focal myocardial infiltration and chronic lymphocytic leukemia.

A 53-year-old female was admitted to the cardiology department on account of signs and symptoms of congestive heart failure (HF) with severe peripheral edema and dyspnea on exertion (New York Heart Association class III) for the past 3 months.