Improve Heart Function Research Articles

Impact of percutaneous coronary intervention on acute echocardiographic parameters in patients with ST-segment elevation myocardial infarction

Abstract Background Transthoracic echocardiography (TTE) provides a rapid, non-invasive, bedside assessment of the cardiac function and hemodynamic condition. It is a valuable tool for the acute clinical evaluation in patients with ST-elevation myocardial infarction (STEMI) at arrival in the catheterization laboratory (cath lab). Purpose To examine the relationship between TTE parameters obtained before and after primary percutaneous coronary intervention (pPCI) in STEMI patients. Method From September 2023 STEMI patients at one tertiary heart center underwent acute bedside TTE examination before pPCI in the cath lab. Patients in cardiogenic shock before leaving the cath lab were excluded. The 5-min focused acute TTE protocol included: LV ejection fraction (LVEF), valvulopathy, mechanical complications, LV outflow tract velocity time integral (LVOT VTI), and diastolic dysfunction (mitral inflow (E and E/A), mitral deceleration time, and mitral annular early diastolic velocity é lateral). The LVEF was categorized in groups: LVEF>45%, moderately reduced (LVEF 35-45%), and severely reduced (LVEF<35%). A full protocol TTE examination was performed before discharge. Results A total of 133 STEMI patients (mean age 63 years, 21% women) were included. Prior to admission, 49% had hypertension, 40% hyperlipidemia, 16% diabetes, 17% chronic ischemic heart disease, and 71% were active or previous smokers. Anterior STEMI was present in 39%, and the median time from cath lab arrival to first wire crossing the culprit lesion was 28 min (IQR 24;38). Vital parameters upon admission were: heart rate 75 bpm (IQR: 66;85), Killip Class 1 (96%), lactate levels 1.6 mM (IQR: 1.2;2.3), and systolic blood pressure of 134±27 mmHg. Considering TTE parameters LVEF and E/A ratio changed significantly from before vs after pPCI (LVEFbefore: 45% vs LVEFafter: 50%, p<0.001 and E/Abefore: 1.1 vs E/Aafter: 0.93, p<0.001), Figure 1. Before pPCI severely reduced LVEF was seen in 17% of patients with improvement in 44% to moderately reduced LVEF, and 4% to normal-slightly reduced LVEF. Before PCI, moderately reduced LVEF was seen in 40% of patients with improvement in 38% to normal-slightly reduced LVEF after PCI. Patients who experienced a decline in LVEF had a longer, though not statistically significant, ECG-to-wire crossing time (119 min [IQR 94;213] vs 102 min [IQR 75;142], p=0.10). Conclusion This study shows that in STEMI patients, the TTE parameters LVEF and E/A ratio were altered after pPCI. Despite a significant decrease in one of the diastolic dysfunction parameters, the E/A ratio remained within the normal range before and after PCI. The increase in LVEF was small, however it may be clinically significant, indicating improved heart function, potentially leading to less symptoms, adjusted treatment plans, and a more favorable prognosis for the patient. However, the parameters should be cautiously interpreted due to measurement uncertainty and validated with a larger sample size. Figure 1. ANCOVA plot

Sodium-dependent glucose transporter 2 inhibitors improve heart function in patients with type 2 diabetes and heart failure.

This article discusses the study by Grubić Rotkvić et al on the mechanisms of action of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) and heart failure (HF). T2DM and HF are highly comorbid, with a significantly increased prevalence of HF in patients with T2DM. SGLT2i exhibit potential in reducing hospitalization rates for HF and cardiovascular mortality through multiple mechanisms, including improving blood glucose control, promoting urinary sodium excretion, reducing sympathetic nervous system activity, lowering both preload and afterload on the heart, alleviating inflammation and oxidative stress, enhancing endothelial function, improving myocardial energy metabolism, and stabilizing cardiac ion homeostasis. Further research and clinical practice will help optimize the use of SGLT2i in HF patients.

Safety and efficacy of catheter ablation in atrial fibrillation patients with heart failure with preserved ejection fraction

PurposeCatheter ablation (CA) for atrial fibrillation (AF) in heart failure patients with preserved ejection fraction (HFPEF) has shown promising results in reducing mortality and improving heart function. However, previous studies have been limited by a lack of control groups and significant heterogeneity in their methodologies.HypothesisCA for AF in HFPEF patients may not increase the complications and had similarly the rate of freedom from AF vs. patients without HFPEF, and it may reduce hospitalizations and mortality and improve heart function VS medical treatment.MethodsThree groups of AF patients were included in the study: 187 patients with HFPEF for their first CA (AFPHF-CA), 187 patients with HFPEF who were undergoing medical therapy (AFPHF-Med), and 196 patients without HFPEF for their first CA (AF-CA).ResultsAfter a mean (± SD) follow-up of 36 ± 3 months, 50.8% of patients in the AFPHF-CA group and 52.0% in the AF-CA group remained in sinus rhythm (P = 0.94), compared to only 12.5% in the AFPHF-Med group (P < 0.001). Age (OR: 1.09, 95% CI: 1.02–1.08, P = 0.016), duration of AF history (OR: 1.01, 95% CI: 1.00-1.02, P = 0.017), left atrial diameter (OR: 1.52, 95% CI: 1.06–2.19, P = 0.024), and the type of atrial fibrillation (OR: 4.02, 95% CI: 1.28–12.62, P = 0.017) were consistent multivariable predictors for sinus rhythm maintenance in AFPHF. HF hospitalization was significantly lower in the AFPHF-CA group (0.38 (0,2)) than in the AFPHF-Med group (1.28(0,3), P < 0.001) during the follow-up. Stroke occurred in 18 of 187 (9.63%) patients in the AFPHF-CA group, significantly lower than the AFPHF-Med group, with approximately 31 of 187 (16.58%) (P < 0.01), but not statistically different from AF-CA, where approximately 17 of 196 (8.67%) experienced stroke (P = 0.65). Regarding mortality, death occurred in 12.8% of patients in the AFPHF-Med group, higher than 7.5% in the AFPHF-CA group and 6.6% in the AF-CA group (P = 0.49). Significant improvements in heart function were observed in the AFPHF-CA group compared to the AFPHF-Med group, including reductions in left ventricular end-diastolic diameter (P < 0.001), New York Heart Association classification (P < 0.001), left ventricular mass index (P < 0.001), and left atrial volume index (P < 0.001). HF hospitalization was significantly lower in the AFPHF-CA group compared to AFPHF-Med (P < 0.001).ConclusionCA for AF has showed significant benefits in patients with HFPEF compared to medical treatment alone. These benefits include improvements in heart function, reduced mortality, incidence of stroke, and hospitalizations. Importantly, CA in HFPEF patients showed comparable maintenance of sinus rhythm (SR) and safety outcomes when compared to CA in individuals with normal heart function.

The highly conserved PIWI-interacting RNA CRAPIR antagonizes PA2G4-mediated NF110-NF45 disassembly to promote heart regeneration in mice.

Targeting the cardiomyocyte cell cycle is a promising strategy for heart repair following injury. Here, we identify a cardiac-regeneration-associated PIWI-interacting RNA (CRAPIR) as a regulator of cardiomyocyte proliferation. Genetic ablation or antagomir-mediated knockdown of CRAPIR in mice impairs cardiomyocyte proliferation and reduces heart regenerative potential. Conversely, overexpression of CRAPIR promotes cardiomyocyte proliferation, reduces infarct size and improves heart function after myocardial infarction. Mechanistically, CRAPIR promotes cardiomyocyte proliferation by competing with NF110 for binding to the RNA-binding protein PA2G4, thereby preventing the interaction of PA2G4 with the NF110-NF45 heterodimer and reducing NF110 degradation. The ability of CRAPIR to promote proliferation was confirmed in human embryonic stem cell-derived cardiomyocytes. Notably, CRAPIR serum levels are lower in individuals with ischemic heart disease and negatively correlate with levels of N-terminal pro-brain natriuretic peptide. These findings position CRAPIR both as a potential diagnostic marker for cardiac injury and as a therapeutic target for heart regeneration through the PA2G4-NF110-NF45 signaling axis.

Morin, as a natural flavonoid, provides promising influences against cardiovascular diseases.

The present investigation evaluated the potential impacts of morin, a natural flavonoid, against cardiovascular disorders. Since inception until September 2024, PubMed, Scopus, and Web of Science have been searched extensively. The process involved eliminating duplicate entries and conducting a systematic review of the remaining studies post-full-text screening. The search was conducted with meticulousness and in adherence to established protocols. Morin has shown various cardioprotective effects in experimental models. It reduces oxidative stress, inflammation, and tissue damage in conditions like myocardial ischemia, injury, and infarction. It also mitigates the harmful effects of toxins and improves hemodynamic parameters, antioxidant levels, and cardiac function. Moreover, it can address conditions like chronic iron overload and metabolic syndrome. Its mechanisms of action involve regulating signaling pathways, promoting autophagy, and reducing oxidative stress and inflammation. Morin hydrate is promising as a therapeutic agent for cardiovascular and related disorders. Morin Hydrate exhibits promising cardioprotective properties, effectively reducing oxidative stress and inflammation in myocardial conditions while also countering the effects of toxins and improving heart function. Additionally, it holds the potential for addressing chronic iron overload and metabolic syndrome. Its multifaceted mechanisms, including signaling pathway regulation and promotion of autophagy, highlight its therapeutic potential for various cardiovascular and related disorders.

Poincaré plot analysis of electrocardiogram uncovers beneficial effects of omaveloxolone in a mouse model of Friedreich ataxia.

Friedreich ataxia (FA) is a rare inherited neuromuscular disorder whereby most patients die of lethal cardiomyopathy and arrhythmias. Mechanisms leading to arrhythmic events in patients with FA are poorly understood. This study aimed to examine cardiac electrical signal propagation in a mouse model of FA with severe cardiomyopathy and to evaluate effects of omaveloxolone (OMAV), the first Food and Drug Administration-approved therapy. Cardiac-specific MCK-Cre frataxin knockout (FXN-cKO) mice were used to mimic FA cardiomyopathy. Invivo surface electrocardiogram (ECG) recordings, Western blotting, quantitative real-time polymerase chain reaction analysis, and histochemistry were performed. Characteristics like long QT syndrome, interatrial block, and ST-segment abnormalities in patients with FA were identified in FXN-cKO mice. FXN-cKO mice exhibited sexual dimorphism in electrical signal propagation and cardiac structural integrity. Untreated FA males showed increased ventricular propagation intervals, whereas females exhibited delayed atrial propagation. OMAV showed no significant therapeutic effect on average ECG time intervals but improved chamber-specific waveforms when aggregated frequency distributions were analyzed. The J wave was absent in FXN-cKO male mice but reappeared with OMAV treatment. Poincaré plots revealed disparate idiopathic arrhythmias with multi-clustering events in individual mice with high incidence in FXN-cKO males. OMAV treatment reduced multi-clustering events to a single cluster; however, autonomic nervous system dysfunction still remained. Our study revealed significant electrical propagation disturbances and sexual dimorphism in FXN-cKO mice with severe cardiomyopathy. Poincaré plots identified irregularities in heart rhythm and autonomic nervous system dysfunction. OMAV improved heart function by stabilizing early repolarization and reducing disparate arrhythmias. This work stresses sex-specific ECG interpretations and alternative mathematical approaches for drug testing in FA models.

Exploring the Relationship Between Ejection Fraction, Arterial Stiffness, NT-proBNP, and Hospitalization Risk in Heart Failure Patients.

Background/Objectives: Heart failure (HF) remains a leading cause of hospitalization and morbidity. Arterial stiffness, measured by pulse wave velocity (PWV) and the augmentation index (AIx), has been linked to HF severity and prognosis. This study investigates the relationship between clinical parameters, biochemical indicators, and arterial stiffness in hospitalized patients with HF, aiming to identify predictors of hospitalization and improve patient management. Methods: This cross-sectional study included 98 patients admitted with HF: 53 with acutely decompensated HF (sudden worsening of symptoms) and 45 with chronic HF (stable symptoms of HF). Clinical and biochemical parameters, including ejection fraction (EF), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, and arterial stiffness indicators (PWV and AIx), were measured at admission. During follow-up, 59 patients required re-hospitalization due to acutely decompensated HF, while 39 remained outpatients without further hospitalization. The relationship between these parameters was analyzed using Pearson correlation coefficients, and multiple Cox regression analysis was conducted to identify independent predictors of re-hospitalization. Results: A significant negative correlation between EF and PWV was found (r = -0.853, 95% CI [-0.910, -0.764]), suggesting an association between improved heart function (higher EF) and reduced arterial stiffness (lower PWV). A moderate positive correlation between EF and AIx (r = 0.626, 95% CI [0.473, 0.805]) suggests that, while higher EF is associated with increased AIx, the relationship is weaker compared to EF and PWV. This may reflect differing contributions of vascular and myocardial factors to HF severity. Hospitalized patients exhibited significantly poorer clinical and biochemical profiles, including higher NT-proBNP levels (p < 0.001) and worse blood pressure (BP) measurements (systolic and diastolic, p < 0.01). Multiple Cox regression analysis identified PWV, Aix, and NT-proBNP as independent predictors of re-hospitalization in HF patients, with significant hazard ratios: PWV (HR = 1.15, p = 0.02), AIx (HR = 1.03, p = 0.02), and NT-proBNP (HR = 1.0001, p < 0.01). Conclusions: Arterial stiffness indices (PWV and AIx), EF, and NT-proBNP were identified as significant predictors of re-hospitalization in HF patients. These findings suggest that integrating arterial stiffness measurements into routine clinical assessments may enhance the risk stratification and inform targeted interventions to reduce hospitalizations and improve outcomes.

Activation of Imprinted Gene PW1 Promotes Cardiac Fibrosis After Ischemic Injury.

Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition in the myocardium, is an important target for heart disease treatments. Pw1 (paternally expressed gene 3) is an imprinted gene expressed from the paternal allele, and de novo purine biosynthesis (DNPB) is a crucial pathway for nucleotide synthesis. However, the roles of PW1 and DNPB in ECM production by cardiac fibroblasts during myocardial ischemia are not yet understood. To induce myocardial damage, we performed left anterior descending coronary artery ligation. We generated Pw1CreER-2A-eGFP and Pw12A-CreER knock-in mouse lines to evaluate the expression of the 2 Pw1 alleles in normal and injured hearts. Bisulfite sequencing was used to analyze the DNA methylation of the Pw1 imprinting control region. We identified the phosphoribosylformylglycinamidine synthase (Pfas) gene, encoding the DNPB enzyme PFAS, as a direct target of PW1 using chromatin immunoprecipitation sequencing and real-time quantitative polymerase chain reaction. The role of DNPB in ECM production and cardiac fibrosis after injury was examined in vitro using cultured cardiac fibroblasts and in vivo with Pfas-deficient mice. Our study demonstrates that myocardial infarction reduces DNA methylation at the imprinting control region of the maternally imprinted gene Pw1, triggering a switch from monoallelic imprinting to biallelic expression of Pw1 in cardiac fibroblasts. In activated cardiac fibroblasts, increased Pw1 expression promotes purine biosynthesis and induces ECM production by transcriptionally activating the DNPB factor Pfas. We identified that DNPB is essential for ECM production in activated fibroblasts and that loss of Pfas in fibroblasts limits cardiac fibrosis and improves heart function after injury. This study demonstrates that Pw1 imprinting is disrupted after injury and reveals a novel role for the downstream target PFAS in ECM production and cardiac fibrogenesis. Targeting the PW1/PFAS signaling pathway presents a promising therapeutic strategy for improving cardiac repair after injury.

Pharmacologically inducing regenerative cardiac cells by small molecule drugs

Adult mammals, unlike some lower organisms, lack the ability to regenerate damaged hearts through cardiomyocytes (CMs) dedifferentiation into cells with regenerative capacity. Developing conditions to induce such naturally unavailable cells with potential to proliferate and differentiate into CMs, that is, regenerative cardiac cells (RCCs), in mammals will provide new insights and tools for heart regeneration research. In this study, we demonstrate that a two-compound combination, CHIR99021 and A-485 (2C), effectively induces RCCs from human embryonic stem cell-derived TNNT2+ CMs in vitro, as evidenced by lineage tracing experiments. Functional analysis shows that these RCCs express a broad spectrum of cardiogenesis genes and have the potential to differentiate into functional CMs, endothelial cells, and smooth muscle cells. Importantly, similar results were observed in neonatal rat CMs both in vitro and in vivo. Remarkably, administering 2C in adult mouse hearts significantly enhances survival and improves heart function post-myocardial infarction. Mechanistically, CHIR99021 is crucial for the transcriptional and epigenetic activation of genes essential for RCC development, while A-485 primarily suppresses H3K27Ac and particularly H3K9Ac in CMs. Their synergistic effect enhances these modifications on RCC genes, facilitating the transition from CMs to RCCs. Therefore, our findings demonstrate the feasibility and reveal the mechanisms of pharmacological induction of RCCs from endogenous CMs, which could offer a promising regenerative strategy to repair injured hearts.

Pharmacologically inducing regenerative cardiac cells by small molecule drugs.

Adult mammals, unlike some lower organisms, lack the ability to regenerate damaged hearts through cardiomyocytes (CMs) dedifferentiation into cells with regenerative capacity. Developing conditions to induce such naturally unavailable cells with potential to proliferate and differentiate into CMs, that is, regenerative cardiac cells (RCCs), in mammals will provide new insights and tools for heart regeneration research. In this study, we demonstrate that a two-compound combination, CHIR99021 and A-485 (2C), effectively induces RCCs from human embryonic stem cell-derived TNNT2+ CMs in vitro, as evidenced by lineage tracing experiments. Functional analysis shows that these RCCs express a broad spectrum of cardiogenesis genes and have the potential to differentiate into functional CMs, endothelial cells, and smooth muscle cells. Importantly, similar results were observed in neonatal rat CMs both in vitro and in vivo. Remarkably, administering 2C in adult mouse hearts significantly enhances survival and improves heart function post-myocardial infarction. Mechanistically, CHIR99021 is crucial for the transcriptional and epigenetic activation of genes essential for RCC development, while A-485 primarily suppresses H3K27Ac and particularly H3K9Ac in CMs. Their synergistic effect enhances these modifications on RCC genes, facilitating the transition from CMs to RCCs. Therefore, our findings demonstrate the feasibility and reveal the mechanisms of pharmacological induction of RCCs from endogenous CMs, which could offer a promising regenerative strategy to repair injured hearts.

Sequential Delivery of Cardioactive Drugs via Microcapped Microneedle Patches for Improved Heart Function in Post Myocardial Infarction Rats

After myocardial infarction, the heart undergoes adverse remodeling characterized by a series of pathological changes, including inflammation, apoptosis, fibrosis, and hypertrophy. In addition to cardiac catheter-based re-establishment of blood flow, patients typically receive multiple medications that aim to address these different mechanisms underlying left ventricular remodeling. The current study aims to establish a versatile multi-drug delivery platform for the controlled and sequential delivery of multiple therapeutic agents in a single treatment. Toward this goal, we generated a microcapped microneedle patch carrying methylprednisolone, interleukin-10, and vascular endothelial growth factor. In vitro characterization demonstrated a time-sequenced release pattern of these drug: methylprednisolone for the first 3 days, interleukin-10 from day 1 to 15, and vascular endothelial growth factor from day 3 to 25. The therapeutic effects of the microneedle patch were evaluated in a rat model of acute myocardial infarction induced by permanent ligation of left anterior descending coronary artery. Heart function was measured using trans-thoracic echocardiography. Heart inflammation, apoptosis, hypertrophy and angiogenesis were evaluated using histology. Our data indicated that, at 28 days after patch transplantation, animals receiving the microneedle patch with sequential release of these three agents showed reduced inflammation, apoptosis and cardiac hypertrophy compared to the animals receiving control patch without sequential release of these agents, which is associated with the improved angiogenesis and heart function. In conclusion, the microneedle patch can be utilized to deliver multiple therapeutic agents in a controlled and sequential manner that aligns with the pathological phases following myocardial infarction. STATEMENT OF SIGNIFICANCE: The post-myocardial infarction heart remodeling is characterized by a series of pathological events including acute inflammation, apoptosis, fibrosis, cardiac hypertrophy, and depressed heart function. In current clinical practice, multiple procedures and drugs given at different time points are necessary to combat these series of pathological events. In this study, we developed a novel microcapped microneedle patch for the controlled sequential delivery of triple cardioprotective drugs aiming to combat acute inflammation and cardiac hypertrophy, and promote angiogenesis. This study presents a comprehensive therapeutic approach, with the microneedle patch addressing multifaceted pathological processes during post-myocardial infarction left ventricular remodeling. This cardiac drug delivery system has the potential to improve patient treatment by delivering drugs in alignment with the series of time-dependent pathological phases following myocardial infarction, ultimately improving clinical outcomes.

The NLRP3-inflammasome inhibitor MCC950 improves cardiac function in a HFpEF mouse model

Heart failure with preserved ejection fraction (HFpEF) is posing a significant medical challenge due to its growing prevalence, high hospitalization rates and limited response to current treatment options. Accumulating evidence suggests that a comorbidity-driven systemic pro-inflammatory state, including activation of the NLRP3 inflammasome, contributes to the pathogenesis of HFpEF. This study aimed to investigate the potential cardiac protective effects of the selective NLRP3 inhibitor MCC950, in a mouse model of HFpEF. HFpEF was obtained in 18–22 months old female mice using high-fat diet (HFD) and angiotensin II (AngII) infusion. Mice developed HFpEF and comorbidities such as obesity, type 2 diabetes, and hypertension. MCC950 was added to HFD and groups were treated for four weeks until the study endpoint. MCC950 treatment resulted in lower plasma IL-18 levels (-47.3 %), illustrating target engagement. First, we observed that MCC950 treatment improved left ventricular function, demonstrated by enhanced global longitudinal strain (GLS, 3.9 %, P<0.01) and reverse peak longitudinal strain (RPLSR, +46.8 %, P<0.05). Second, MCC950 reduced cardiac hypertrophy (cardiomyocyte size -19.5 %, P<0.001) and fibrosis (-32.5 %, P<0.05), accompanied by lower expression of pro-fibrotic genes. Finally, MCC950 treatment reduced macrophage infiltration in left ventricular tissue and attenuated macrophage accumulation in visceral adipose tissue, even more as compared to caloric restriction. Overall, this suggests that NLRP3 inhibition could be a promising treatment for HFpEF patients with a pro-inflammatory profile, potentially improving heart function, systemic inflammation, and metabolic parameters.

Abstract 4139176: SUMOylation of TP53INP1 Is Involved in miR-30a-5p-Regulated Heart Senescence

Introduction: During natural aging, physiological remodeling of the heart is a critical for the cardiovascular disease and heart failure. miR-30a-5p is related to kidney injury, cancer, and autoimmune diseases. However, whether miR-30a-5p has an effect in cardiac aging has yet to be explored. Hypothesis: This study aimed to characterize the role and mechanism of action of miR-30a-5p in cardiac senescence. Methods: We established miR-30a-5p knockout/overexpressing mouse model. Natural heart aging (18-months-old) and D-galactose-induced aging mouse model were established. The mechanism was explored in D-galactose- or 10-days-cultured cardiomyocytes. Results: miR-30a-5p was downregulated in aged mouse hearts and neonatal rat cardiomyocytes (NRCMs). In vivo, using a combination of echocardiography and different molecular biological approaches, we investigated the role of miR-30a-5p knockout or overexpressed mice on natural- or D-galactose-induced heart aging. In vitro, using RNA-sequence and a series of molecular biology, the mechanism of miR-30a-5p-regulated cardiac senescence was explored in cardiomyocytes. miR-30a-5p knockout mice showed aggravated natural- or D-galactose-induced heart aging compared to wild-type littermate mice, with significantly decreased heart function, increased number of γH2AX-positive cells, reduced telomere length, and upregulated p21 and p53 expression. Cardiac-specific knockdown of miR-30a-5p using adeno-associated virus 9 in D-galactose-induced senescent wild-type mice showed effects similar to those observed in knockout mice. Notably, overexpression of miR-30a-5p in wild-type murine hearts alleviated D-galactose-induced heart senescence by improving heart function, increasing telomere length, decreasing the number of γH2AX-positive cells, and downregulating p53 and p21 expression. This was confirmed in D-galactose-treated or naturally aged NRCMs. Mechanistically, TP53INP1 was identified as a target of miR-30a-5p by mediating the SUMOylation of TP53INP1 and its translocation from the cytoplasm to the nucleus to interact with p53. Further evidence demonstrated that cardiac-specific TP53INP1 deficiency ameliorates miR-30a-5p knockout-aggravated cardiac dysfunction and heart senescence. Conclusions: This study identified miR-30a-5p as a crucial modulator of heart senescence and revealed that the miR-30a-5p–TP53INP1–p53 axis is essential for heart and cardiomyocyte aging.

Heart function enhancement by an Nrf2-activating antioxidant in acute Y-strain Chagas disease, but not in chronic Colombian or Y-strain.

Oxidative stress promotes T. cruzi growth and development of chronic Chagas heart dysfunction. However, the literature contains gaps that must be fulfilled, largely due to variations in parasite DTU sources, cell types, mouse strains, and tools to manipulate redox status. We assessed the impact of oxidative environment on parasite burden in cardiomyoblasts and the effects of the Nrf2-inducer COPP on heart function in BALB/c mice infected with either DTU-II Y or DTU-I Colombian T. cruzi strains. Treatment with antioxidants CoPP, apocynin, resveratrol, and tempol reduced parasite burden in cardiomyoblasts H9C2 for both DTUI- and II-strains, while H2O2 increased it. CoPP treatment improved electrical heart function when administered during acute stage of Y-strain infection, coinciding with an overall trend towards increased survival and reduced heart parasite burden. These beneficial effects surpassed those of trypanocidal benznidazole, implying that CoPP directly affects heart physiology. CoPP treatment had beneficial impact on heart systolic function when performed during acute and evaluated during chronic stage. No impact of CoPP on heart parasite burden, electrical, or mechanical function was observed during the chronic stage of Colombian-strain infection, despite previous demonstrations of improvement with other antioxidants. Treatment with CoPP also did not improve heart function of mice chronically infected with Y-strain. Our findings indicate that amastigote growth is responsive to changes in oxidative environment within heart cells regardless of the DTU source, but CoPP influence on heart parasite burden in vivo and heart function is mostly confined to the acute phase. The nature of the antioxidant employed, T. cruzi DTU, and the stage of disease, emerge as crucial factors to consider in heart function studies.

SUMOylation of TP53INP1 is involved in miR-30a-5p-regulated heart senescence

Heart senescence is critical for cardiac function. This study aimed to characterize the role and mechanism of action of miR-30a-5p in cardiac senescence. miR-30a-5p was downregulated in aged mouse hearts and neonatal rat cardiomyocytes (NRCMs). In vivo, using a combination of echocardiography and different molecular biological approaches, we investigated the role of miR-30a-5p knockout or overexpression in natural- or D-galactose-induced heart aging in mice. In vitro, using RNA sequencing and a series of molecular biology methods, the mechanism by which miR-30a-5p regulates cardiac senescence was explored in cardiomyocytes. miR-30a-5p knockout mice showed aggravated natural- or D-galactose-induced heart aging compared to wild-type littermate mice, with significantly decreased heart function, an increased number of γH2AX-positive cells, reduced telomere length, and upregulated p21 and p53 expression. Cardiac-specific knockdown of miR-30a-5p using adeno-associated virus 9 in D-galactose-induced senescent wild-type mice resulted in effects similar to those observed in knockout mice. Notably, the overexpression of miR-30a-5p in wild-type murine hearts alleviated D-galactose-induced heart senescence by improving heart function, increasing telomere length, decreasing the number of γH2AX-positive cells, and downregulating p53 and p21 expression. This was confirmed in D-galactose-treated or naturally aged NRCMs. Mechanistically, TP53INP1 was identified as a target of miR-30a-5p by mediating the SUMOylation of TP53INP1 and its translocation from the cytoplasm to the nucleus to interact with p53. Furthermore, this study demonstrated that cardiac-specific TP53INP1 deficiency ameliorates miR-30a-5p knockout-aggravated cardiac dysfunction and heart senescence. This study identified miR-30a-5p as a crucial modulator of heart senescence and revealed that the miR-30a-5p–TP53INP1–p53 axis is essential for heart and cardiomyocyte aging.

Bone-marrow macrophage-derived GPNMB protein binds to orphan receptor GPR39 and plays a critical role in cardiac repair.

Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane protein initially identified in nonmetastatic melanomas and has been associated with human heart failure; however, its role in cardiac injury and function remains unclear. Here we show that GPNMB expression is elevated in failing human and mouse hearts after myocardial infarction (MI). Lineage tracing and bone-marrow transplantation reveal that bone-marrow-derived macrophages are the main source of GPNMB in injured hearts. Using genetic loss-of-function models, we demonstrate that GPNMB deficiency leads to increased mortality, cardiac rupture and rapid post-MI left ventricular dysfunction. Conversely, increasing circulating GPNMB levels through viral delivery improves heart function after MI. Single-cell transcriptomics show that GPNMB enhances myocyte contraction and reduces fibroblast activation. Additionally, we identified GPR39 as a receptor for circulating GPNMB, with its absence negating the beneficial effects. These findings highlight a pivotal role of macrophage-derived GPNMBs in post-MI cardiac repair through GPR39 signaling.

Performance of the novel ANTWERP score in predicting heart function improvement after atrial fibrillation ablation in Asian patients with heart failure.

Previous research has demonstrated that atrial fibrillation (AF) ablation improves heart function variably among patients. We proposed that the ANTWERP score, which was validated in a European group of patients with low left ventricular ejection fraction (LVEF) who had AF ablation, would be valid in an Asian group as well. The purpose of the study is to examine how well a new scoring system (the ANTWERP score) can predict heart function improvement after atrial fibrillation ablation in Asian patients with heart failure. A retrospective review was conducted on patients (n = 84) undergoing AF ablation between January 2019 and June 2022. Initial diagnoses for impaired LV systolic function were confirmed by echocardiography. Patients meeting the "2021 Universal Definition of HF" criteria for LVEF recovery were classified as "responders." Similarities were observed between responders and nonresponders regarding comorbidities, AF type, and LVEF, except for the left ventricular internal diameter in diastole. A higher percentage of responders had an ANTWERP score ≤2 (87.8%) compared to those with a score >2 (55.6%). LVEF improvement was notably higher in the former group (+14.8% vs. +9.4%, p = .043). Atrial reverse remodeling and recurrent atrial arrhythmia rates were similar across groups. The conclusion of the study was that the ANTWERP score effectively predicted LVEF improvement after atrial fibrillation ablation in the Asian population and that this scoring system could be used to guide clinical decisions and prognosis prediction.

Chronic Activation of Tubulin Tyrosination Improves Heart Function.

Hypertrophic cardiomyopathy (HCM) is the most common cardiac genetic disorder caused by sarcomeric gene variants and associated with left ventricular hypertrophy and diastolic dysfunction. The role of the microtubule network has recently gained interest with the findings that microtubule detyrosination (dTyr-MT) is markedly elevated in heart failure. Acute reduction of dTyr-MT by inhibition of the detyrosinase (VASH [vasohibin]/SVBP [small VASH-binding protein] complex) or activation of the tyrosinase (TTL [tubulin tyrosine ligase]) markedly improved contractility and reduced stiffness in human failing cardiomyocytes and thus posed a new perspective for HCM treatment. In this study, we tested the impact of chronic tubulin tyrosination in an HCM mouse model (Mybpc3 knock-in), in human HCM cardiomyocytes, and in SVBP-deficient human engineered heart tissues (EHTs). Adeno-associated virus serotype 9-mediated TTL transfer was applied in neonatal wild-type rodents, in 3-week-old knock-in mice, and in HCM human induced pluripotent stem cell-derived cardiomyocytes. We show (1) TTL for 6 weeks dose dependently reduced dTyr-MT and improved contractility without affecting cytosolic calcium transients in wild-type cardiomyocytes; (2) TTL for 12 weeks reduced the abundance of dTyr-MT in the myocardium, improved diastolic filling, compliance, cardiac output, and stroke volume in knock-in mice; (3) TTL for 10 days normalized cell area in HCM human induced pluripotent stem cell-derived cardiomyocytes; (4) TTL overexpression activated transcription of tubulins and other cytoskeleton components but did not significantly impact the proteome in knock-in mice; (5) SVBP-deficient EHTs exhibited reduced dTyr-MT levels, higher force, and faster relaxation than TTL-deficient and wild-type EHTs. RNA sequencing and mass spectrometry analysis revealed distinct enrichment of cardiomyocyte components and pathways in SVBP-deficient versus TTL-deficient EHTs. This study provides the first proof of concept that chronic activation of tubulin tyrosination in HCM mice and in human EHTs improves heart function and holds promise for targeting the nonsarcomeric cytoskeleton in heart disease.

The Impacts of Cardiac Rehabilitation Exercise Therapy in Patients Following Percutaneous Coronary Intervention: Systematic Review

Abstract Objective: This study focused on establishing the impact of cardiac rehabilitation (CR) exercise therapy following percutaneous coronary intervention (PCI) with multiple vital outcomes. Methods: A comprehensive search was performed across databases, including ScienceDirect, PubMed, PMC, and Cochrane, with a restriction to the English-language articles. The focus was on randomized controlled trials (RCTs) that evaluated the effects of CR exercise therapy in patients who underwent PCI – comparing the group that participated in CR exercise therapy with those that received routine care. Key outcomes evaluated included laboratory values, left ventricular ejection fraction, 6-min walk test, quality of life (QoL), cardiopulmonary function, exercise capacity, and cardiovascular events. The Cochrane RoB 2 was utilized to evaluate the quality of the study. Outcomes were synthesized qualitatively to summarize the effects of CR on the estimated parameters. Results: This review included 12 RCTs from several countries involving 1215 patients – 605 in control groups and 610 in intervention groups. Nine studies categorized some concerns in the overall assessment, and three RCTs were classified as low risk of bias. Results showed that patients with CR intervention effectively experience positive impacts across all key outcomes. Conclusion: CR benefits coronary artery disease patients post-PCI by managing cardiovascular risk factors, improving heart function, reducing cardiovascular events, and enhancing QoL.

Effect of sacubitril and valsartan combined with conventional therapy on patients with heart failure

Purpose: To investigate the clinical effectiveness of the combination of sacubitril and valsartan with conventional therapy in the treatment of patients with heart failure. Methods: This was a retrospective study comprising 100 heart failure patients randomized into study (n = 57) and control groups (n = 43). The study group received sacubitril/valsartan along with conventional drug therapy while control group received only conventional drugs, viz, irbesartan, metoprolol slow release, and furosemide tablets. Echocardiogram showing left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), left anterior descending artery (LAD), Nterminal pro-b-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), glomerular filtration rate (eGFR), and homocysteine (HCY) of the two groups were compared before and after treatment. Multiple regression was used to analyze the correlation between re-hospitalization and sacubitril/valsartan intervention. Results: The study group showed significantly lower LVEF, LVESD, LVEDD, LAD, NT-proBNP, and homocysteine levels after treatment compared to control group (p &lt; 0.05). Re-hospitalization for abnormal cardiovascular events between the two groups was significantly different in the adjusted Cox proportional hazards regression model. Furthermore, multiple regression analysis showed that sacubitril/valsartan treatment was the independent variable (p &lt; 0.001). Conclusion: Sacubitril/valsartan improves heart function, with reduced incidence of adverse effects without affecting renal function. Further studies are required to validate these findings by expanding sample size, strictly controlling data quality and strengthening follow-up.