Chronic Cardiac Dysfunction Research Articles

Improving Outcomes in Peripartum Cardiomyopathy with Vericiguat: A Clinical Case

Peripartum cardiomyopathy (PPCM) is a specific form of cardiomyopathy that manifests toward the end of pregnancy or within 5 months postpartum, characterized by a decrease in cardiac output due to impaired myocardial function. This condition has a multifactorial origin, influenced by genetic predispositions, inflammatory processes, autoimmunity, hormonal variations, and nutritional deficiencies. Prognosis varies among patients: while some recover completely within 6 months, others may develop chronic cardiac dysfunction requiring long-term treatment. Vericiguat, a soluble guanylate cyclase stimulator, has shown promising results in the treatment of heart failure with reduced ejection fraction. This drug works by enhancing the nitric oxide signaling pathway, promoting vasodilation, and improving myocardial function. Although the use of vericiguat in PPCM is not yet fully documented, its potential benefits suggest that it may represent a valid therapeutic option when standard therapies are insufficient for symptom control. We present the case of a 32-year-old woman with PPCM, initially undiagnosed, who developed severe symptoms of dyspnea, orthopnea, and peripheral edema postpartum. These symptoms were accompanied by a significant reduction in left ventricular ejection fraction. Following a suboptimal response to standard heart failure therapy, vericiguat was incorporated into her treatment regimen. In subsequent outpatient follow-ups, the patient‘s symptoms progressively improved, and left ventricular systolic function markedly increased. The patient became asymptomatic and was able to resume her normal daily activities. While this case suggests that vericiguat could be an effective adjunctive treatment for PPCM, it remains unclear whether these improvements were directly attributable to vericiguat or could have occurred with continued standard therapy alone. Further studies are needed to define the role of vericiguat in this condition.

Microparticle Mediated Delivery of Apelin Improves Heart Function in Post Myocardial Infarction Mice.

Apelin is an endogenous prepropeptide that regulates cardiac homeostasis and various physiological processes. Intravenous injection has been shown to improve cardiac contractility in patients with heart failure. However, its short half-life prevents studying its impact on left ventricular remodeling in the long term. Here, we aim to study whether microparticle-mediated slow release of apelin improves heart function and left ventricular remodeling in mice with myocardial infarction (MI). A cardiac patch was fabricated by embedding apelin-containing microparticles in a fibrin gel scaffold. MI was induced via permanent ligation of the left anterior descending coronary artery in adult C57BL/6J mice followed by epicardial patch placement immediately after (acute MI) or 28 days (chronic MI) post-MI. Four groups were included in this study, namely sham, MI, MI plus empty microparticle-embedded patch treatment, and MI plus apelin-containing microparticle-embedded patch treatment. Cardiac function was assessed by transthoracic echocardiography. Cardiomyocyte morphology, apoptosis, and cardiac fibrosis were evaluated by histology. Cardioprotective pathways were determined by RNA sequencing, quantitative polymerase chain reaction, and Western blot. The level of endogenous apelin was largely reduced in the first 7 days after MI induction and it was normalized by day 28. Apelin-13 encapsulated in poly(lactic-co-glycolic acid) microparticles displayed a sustained release pattern for up to 28 days. Treatment with apelin-containing microparticle-embedded patch inhibited cardiac hypertrophy and reduced scar size in both acute and chronic MI models, which is associated with improved cardiac function. Data from cellular and molecular analyses showed that apelin inhibits the activation and proliferation of cardiac fibroblasts by preventing transforming growth factor-β-mediated activation of Smad2/3 (supporessor of mothers against decapentaplegic 2/3) and downstream profibrotic gene expression. Poly(lactic-co-glycolic acid) microparticles prolonged the apelin release time in the mouse hearts. Epicardial delivery of the apelin-containing microparticle-embedded patch protects mice from both acute and chronic MI-induced cardiac dysfunction, inhibits cardiac fibrosis, and improves left ventricular remodeling.

Extracellular Vesicles Derived from Human Liver Stem Cells Counteract Chronic Kidney Disease Development and Cardiac Dysfunction in Remnant Kidney Murine Model: The Possible Involvement of Proteases.

Fibrosis is a marker of chronic kidney disease (CKD) and consists of the accumulation of the extracellular matrix (ECM) components, causing the progressive deterioration of kidney function. Human liver stem cells (HLSCs) have anti-fibrotic activity, and HLSC-derived extracellular vesicles (EVs) mediate this effect. Herein, we evaluated the ability of HLSC-EVs to reverse renal and cardiac alterations in a murine model of partial nephrectomy (PNx) that mimics human CKD development. Furthermore, we investigated the contribution of extracellular matrix remodeling-related proteases to the anti-fibrotic effect of HLSC-EVs. PNx was performed by ligation of both poles of the left kidney, followed one week later by the removal of the right kidney. EV treatment started 4 weeks after the nephrectomy, when renal and cardiac alternations were already established, and mice were sacrificed at week eight. HLSC-EV treatment improved renal function and morphology, significantly decreasing interstitial fibrosis, glomerular sclerosis, and capillary rarefaction. This improvement was confirmed by the decreased expression of pro-fibrotic genes. Moreover, EV treatment improved cardiac function and reduced cardiac fibrosis. HLSC-EVs shuttled different proteases with ECM remodeling activity, and matrix metalloproteinase 1 (MMP-1) was involved in their anti-fibrotic effect on renal tissue. HLSC-EV treatment interferes with CKD development and ameliorates cardiomyopathy in PNx mice.

Understanding the pathobiology of intermediate filaments to curb acute and chronic cardiac dysfunction

Understanding the pathobiology of intermediate filaments to curb acute and chronic cardiac dysfunction

Protective Role of Dioscin against Doxorubicin-Induced Chronic Cardiotoxicity: Insights from Nrf2-GPX4 Axis-Mediated Cardiac Ferroptosis.

Recent evidence suggests that ferroptosis, an iron-facilitated cell death with excessive lipid peroxidation, is a critical mechanism underlying doxorubicin (DOX)-induced cardiotoxicity (DIC). Although dioscin has been reported to improve acute DIC, direct evidence is lacking to clarify the role of dioscin in chronic DIC and its potential mechanism in cardiac ferroptosis. In this study, we used chronic DIC rat models and H9c2 cells to investigate the potential of dioscin to mitigate DIC by inhibiting ferroptosis. Our results suggest that dioscin significantly improves chronic DIC-induced cardiac dysfunction. Meanwhile, it significantly inhibited DOX-induced ferroptosis by reducing Fe2+ and lipid peroxidation accumulation, maintaining mitochondrial integrity, increasing glutathione peroxidase 4 (GPX4) expression, and decreasing acyl-CoA synthetase long-chain family 4 (ACSL4) expression. Through transcriptomic analysis and subsequent validation, we found that the anti-ferroptotic effects of dioscin are achieved by regulating the nuclear factor-erythroid 2-related factor 2 (Nrf2)/GPX4 axis and Nrf2 downstream iron metabolism genes. Dioscin further downregulates nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and upregulates expression of frataxin (FXN) and ATP-binding cassette B8 (ABCB8) to limit mitochondrial Fe2+ and lipid peroxide accumulation. However, Nrf2 inhibition diminishes the anti-ferroptotic effects of dioscin, leading to decreased GPX4 expression and increased lipid peroxidation. This study is a compelling demonstration that dioscin can effectively reduce DIC by inhibiting ferroptosis, which is dependent on the Nrf2/GPX4 pathway modulation.

Deciphering the Receptor-Mediated Signaling Pathways of Interleukin-19 and Interleukin-20.

Interleukin-19 (IL-19) and Interleukin-20 (IL-20) are inflammatory cytokines belonging to the IL-10 family with immunoregulatory properties. Emerging evidence highlights the importance of association of these cytokines with both immunological and inflammatory disorders, including chronic inflammation, cardiac dysfunction, and cancer. IL-19 and IL-20 bind to the heterodimeric receptor complex and induce multiple downstream signaling cascades by activating the signal transducer and activator of transcription 3 (STAT3), Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT1), and NFKB inhibitor alpha (NFKBIA), leading to proinflammatory and anti-inflammatory reactions in cancer, inflammation, tumor microenvironment, and infectious diseases. Considering the significant role of these cytokines, we integrated its cellular signaling network by combining multiomics molecular events associated with 56 molecules of induced by IL-19 and 156 molecules of by IL-20. The reactions of these signaling events are classified into enzyme catalysis/post-translational modifications, activation/inhibition events, molecular associations, gene regulations at the mRNA and protein level, and the protein translocation events. We believe that this signaling pathway map would serve as a knowledge base, that aid researchers and clinicians to understand and explore the intricate mechanisms and identify novel signaling components and therapeutic targets for diseases associated with dysregulated IL-19 and IL-20 signaling.

Beclin 1 Haploinsufficiency Ameliorates High-Fat Diet-Induced Myocardial Injury via Inhibiting Alternative Mitophagy.

Aims: Mitochondrial homeostasis is essential for maintaining redox balance. Besides canonical autophagy, Rab9-dependent alternative autophagy is a crucial mechanism in metabolic cardiomyopathy. Here, we aim to investigate the role of alternative mitophagy and Beclin 1 haploinsufficiency (Beclin 1+/-) in high-fat diet (HFD)-induced metabolic cardiomyopathy. Results: Twenty-four-week HFD impaired glucose tolerance and cardiomyocyte contraction in wild-type mice, both of which were rescued in Beclin 1+/- mice. Beclin 1 haploinsufficiency had little effect on the conventional autophagy mediators (ATG5, LC3 II/LC3 I) but further upregulated Rab9 expression, a marker of alternative autophagy, in response to HFD challenge. Furthermore, either the inhibition of alternative autophagy or Beclin 1 haploinsufficiency abolished palmitic acid (PA)-induced cardiomyocyte contractile anomalies. In vitro, PA overactivated mitophagy, resulting in decreased mitochondrial content in H9C2 cells. These aberrations were alleviated in cells deficient in alternative autophagy but not in cells deficient in conventional autophagy. Mechanistically, HFD promoted reactive oxygen species (ROS) production, activated Rab9-dependent alternative mitophagy, and inhibited mitochondrial biosynthesis. Beclin 1+/- rescued HFD-induced ROS overflow, mitochondrial biogenesis impairment, and prevented Rab9 translocation from the cytoplasm to the mitochondria, thereby inhibiting Rab9-mediated mitophagy overactivation. Innovation: For the first time, this study suggests that prolonged alternative mitophagy exacerbates chronic HFD-induced cardiac dysfunction and supports the protective role of Beclin 1 haploinsufficiency in metabolic cardiomyopathy. This provides additional evidence for a target-based pharmacological intervention. Conclusion: Beclin 1 haploinsufficiency protects against HFD-induced cardiac dysfunction by inhibiting Rab9-dependent alternative mitophagy and ROS production, while promoting mitochondrial biogenesis. Modulating Beclin 1 expression holds promise in preventing chronic HFD-related cardiomyopathy.

A comprehensive review of heart failure: Unraveling the etiology, decoding pathophysiological mechanisms, navigating diagnostic modalities, exploring pharmacological interventions, advocating lifestyle modifications, and charting the horizon of emerging therapies in the complex landscape of chronic cardiac dysfunction.

Heart failure (HF) poses a significant global health burden, necessitating a profound understanding of its multifaceted dimensions. This comprehensive review aims to unravel the etiology, decode pathophysiological mechanisms, navigate diagnostic modalities, explore pharmacological interventions, advocate lifestyle modifications, and chart the horizon of emerging therapies in the complex landscape of chronic cardiac dysfunction. The exploration of HF begins with an insightful journey into its diverse etiological factors, encompassing genetic predispositions, hypertension, and coronary artery disease. Delving into pathophysiological mechanisms, this review elucidates the intricate processes of cardiac remodeling, neurohormonal activation, and cellular dysfunction that underlie the progression of HF. Diagnostic modalities play a pivotal role in unraveling the mysteries of HF by examining advanced imaging techniques, biomarkers, and comprehensive clinical assessments. The pharmacological interventions section provides an in-depth analysis of traditional medications, such as diuretics and angiotensin-converting enzyme inhibitors, while highlighting the emergence of novel drug classes transforming HF management. Advocating lifestyle modifications emphasizes the crucial role of diet, exercise, smoking cessation, and alcohol moderation in enhancing patient outcomes. Lastly, the review delves into the promising horizon of emerging therapies, offering a glimpse into current research, innovative treatment approaches, and potential breakthroughs. As HF management faces challenges in patient compliance, healthcare access, and education, this comprehensive review aims to equip healthcare professionals and researchers with a holistic understanding of chronic cardiac dysfunction's intricacies. In conclusion, synthesizing key findings emphasizes the need for an integrated and multidimensional approach to effectively address the complex landscape of heart failure.

The New Trends in Physiological and Pathological Actions of Ghrelin (Brain-Heart Axis) on the Heart and Cardiovascular System

Background: Ghrelin increased significantly the Left Ventriculus Eject Fraction and end-systolic volume after 30 minutes of intra-venous injection and without alterations heart rate and blood pressure. Ghrelin was discovered in 1999 as an only one 28 amino acid peptides (with octanoyl serine group) located on the short arm of chromosome 3 (position 3p25-26) having six exons, two are noncoding and four introns and encodes a 511 bp mRNA. Ghrelin is synthesized by the endocrine X/A-like cells located from the gastric fundus mucosa through the whole mucosa of the medium right vertical side of the stomach until to the 1 inch before anatomical pylorus. These cells are responsible to produced 80% of the whole ghrelin produced in the human body. Furthermore, other place of this production occurs at the hypothalamus, the pituitary, second portion of duodenum, pancreas, heart and other tissues. Bibliographic references also demonstrate the importance of ghrelin’s action in the main cardiovascular activities. Related to cardiovascular activities, ghrelin plays multitudinous beneficial and thereby help during cardiovascular diseases. Several studies demonstrated that ghrelin cause an anti-inflammatory activity by the inhibition of proinflammatory cytokines which can diminish inflammatory diseases in the heart, pericardium and specific innervations, for instance, vagus nerve and inhibited sympathetic nerves. Outcomes of this review emphasize these important actions of ghrelin. Methods: A systematic review of ghrelin activities over the heart and cardiovascular system with the inclusion of papers in review involved the physiological and physio pathological activities of ghrelin in vivo and in vitro studies. Results: Ghrelin is a natural tide with the growth hormone secretagogue (GHS) receptor (GHS-R) which cloned in 1996. The processes which generate this peptide and ghrelin-related peptides are transcriptional, translational and posttranslational. Homo and heterodimers of GHS-R and other yet unidentified receptors mediate the biological actions of acyl ghrelin and desacyl ghrelin. However, the main biological functions of ghrelin involve the secretion of growth hormone, stimulation of appetite and food intake at the hypothalamus, modulate acid secretion and motility, endocrine and exocrine pancreas secretion, blockaded insulin activity, heart functions and cardiovascular responses and other. Conclusion: One of the main occurrences in acute heart infarction is an increase activation of cardiac sympathetic nerve activity (CSNA) which is one of the causes of chronic cardiac dysfunction (CCD). Ghrelin is an effective for obtain a better cardiac function and by the suppression of renal sympathetic nerve activity which also have an important benefit to the acute myocardial infarction. Therefore, the physiological effects of ghrelin are very important to the body homeostasis even in the grave heart and cardiovascular diseases and in the immunological system.

Voltage-dependent anion channel 1 (VDAC1) overexpression alleviates cardiac fibroblast activation in cardiac fibrosis via regulating fatty acid metabolism

Cardiac fibrosis is characterized by the excessive deposition of extracellular matrix in the myocardium with cardiac fibroblast activation, leading to chronic cardiac remodeling and dysfunction. However, little is known about metabolic alterations in fibroblasts during cardiac fibrosis, and there is a lack of pharmaceutical treatments that target metabolic dysregulation. Here, we provided evidence that fatty acid β-oxidation (FAO) dysregulation contributes to fibroblast activation and cardiac fibrosis. With transcriptome, metabolome, and functional assays, we demonstrated that FAO was downregulated during fibroblast activation and cardiac fibrosis, and that perturbation of FAO reversely affected the fibroblast-to-myofibroblast transition. The decrease in FAO may be attributed to reduced long-chain fatty acid (LCFA) uptake. Voltage-dependent anion channel 1 (VDAC1), the main gatekeeper of the outer mitochondrial membrane (OMM), serves as the transporter of LCFA into the mitochondria for further utilization and has been shown to be decreased in myofibroblasts. In vitro, the addition of exogenous VDAC1 was shown to ameliorate cardiac fibroblast activation initiated by transforming growth factor beta 1 (TGF-β1) stimuli, and silencing of VDAC1 displayed the opposite effect. A mechanistic study revealed that VDAC1 exerts a protective effect by regulating LCFA uptake into the mitochondria, which is impaired by an inhibitor of carnitine palmitoyltransferase 1A. In vivo, AAV9-mediated overexpression of VDAC1 in myofibroblasts significantly alleviated transverse aortic constriction (TAC)-induced cardiac fibrosis and rescued cardiac function in mice. Finally, we treated mice with the VDAC1-derived R-Tf-D-LP4 peptide, and the results showed that R-Tf-D-LP4 prevented TAC-induced cardiac fibrosis and dysfunction in mice. In conclusion, this study provides evidence that VDAC1 maintains FAO metabolism in cardiac fibroblasts to repress fibroblast activation and cardiac fibrosis and suggests that the VDAC1 peptide is a promising drug for rescuing fibroblast metabolism and repressing cardiac fibrosis.

Acetylcholine receptor agonists effectively attenuated multiple program cell death pathways and improved left ventricular function in trastuzumab-induced cardiotoxicity in rats

AimsCardiotoxicity is a seriously debilitating complication of trastuzumab (TRZ) therapy in patients with cancer as a consequence of overexpression of the human epidermal growth factor receptor 2. Although most TRZ-induced cardiotoxicity (TIC) cases are reversible, some patients experience chronic cardiac dysfunction, and these irreversible concepts may be associated with cardiomyocyte death. Acetylcholine receptor (AChR) activation has been shown to exert cardioprotection in several heart diseases, but the effects of AChR agonists against TIC have not been investigated. Main methodForty adult male Wistar rats were randomized into 5 groups: (i) CON (0.9 % normal saline), (ii) TRZ (4 mg/kg/day), (iii) TRZ + α7nAChR agonist (PNU-282987: 3 mg/kg/day), (iv) TRZ + mAChR agonists (bethanechol: 12 mg/kg/day), and (v) TRZ + combined treatment (Combined PNU-282987 and bethanechol). Key findingsThe progression of TIC was driven by mitochondrial dysfunction, autophagic deficiency, and excessive myocyte death including by pyroptosis, ferroptosis, and apoptosis, which were significantly alleviated by α7nAChR and mAChR agonists. Interestingly, necroptosis was not associated with development of TIC. More importantly, the in vitro study validated the cytoprotective effects of AChR activation in TRZ-treated H9c2 cells, while not interfering with the anticancer properties of TRZ. All of these findings indicated that TRZ induced mitochondrial dysfunction, autophagic deficiency, and excessive myocyte death including pyroptosis, ferroptosis, and apoptosis, leading to impaired cardiac function. These pathological alterations were attenuated by α7nAChR and mAChR agonists. Significanceα7nAChR and mAChR agonists might be used as a future therapeutic target in the mitigation of TIC.

End-stage care for children after heart transplant.

Heart transplant is performed annually in over 600 children worldwide to treat life-limiting cardiac disease. Conversations regarding waitlist mortality, post-transplant morbidity and mortality, and goals of care are commonplace pre-transplant. However, there is a void of information and resources for providers and families when end-stage disease recurs in the long-term transplant recipient. The purpose of this review is to discuss the care of the pediatric heart transplant recipient with chronic cardiac dysfunction occurring years after a successful transplant. This includes a need for transplant providers to have education and training related both to palliative care and medical ethics to improve shared decision making with patients and families.

Semaphorin3A Exacerbates Cardiac Microvascular Rarefaction in Pressure Overload-Induced Heart Disease.

Microvascular endothelial cells (MiVECs) impair angiogenic potential, leading to microvascular rarefaction, which is a characteristic feature of chronic pressure overload-induced cardiac dysfunction. Semaphorin3A (Sema3A) is a secreted protein upregulated in MiVECs following angiotensin II (Ang II) activation and pressure overload stimuli. However, its role and mechanism in microvascular rarefaction remain elusive. The function and mechanism of action of Sema3A in pressure overload-induced microvascular rarefaction, is explored, through an Ang II-induced animal model of pressure overload. RNA sequencing, immunoblotting analysis, enzyme-linked immunosorbent assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and immunofluorescence staining results indicate that Sema3A is predominantly expressed and significantly upregulated in MiVECs under pressure overload. Immunoelectron microscopy and nano-flow cytometry analyses indicate small extracellular vesicles (sEVs), with surface-attached Sema3A, to be a novel tool for efficient release and delivery of Sema3A from the MiVECs to extracellular microenvironment. To investigate pressure overload-mediated cardiac microvascular rarefaction and cardiac fibrosis in vivo, endothelial-specific Sema3A knockdown mice are established. Mechanistically, serum response factor (transcription factor) promotes the production of Sema3A; Sema3A-positive sEVs compete with vascular endothelial growth factor A to bind to neuropilin-1. Therefore, MiVECs lose their ability to respond to angiogenesis. In conclusion, Sema3A is a key pathogenic mediator that impairs the angiogenic potential of MiVECs, which leads to cardiac microvascular rarefaction in pressure overload-induced heart disease.

Therapeutic Development of Levosimendan in Acute and Advanced Heart Failure: A Systematic Review.

Levosimendan (LS) has been progressively used for the treatment of patients developing acute as well as chronic or advanced cardiac dysfunction. It has proven to be a better inotropic agent than its counterparts in terms of its ability to increase the cardiac output in an acutely or chronically decompensated heart without an increase in the myocardial oxygen demand. The purpose of this systematic review, which was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020, was to determine the efficacy and advantages of utilizing LS in patients with both acute and chronic heart failure. We collected and reviewed articles, including clinical trials, literature reviews, randomized and non-randomized control trials, case-control and cohort studies, and systematic reviews and meta-analyses published between January 1, 2012, and November 27, 2022. The databases that were used to collect these articles included Pubmed, Pubmed Central, Cochrane Library, and Google Scholar. After applying appropriate filters, a total of 143 reports were identified from these four databases. They were further screened and subjected to quality assessment tools which finally yielded 21 studies that were included in this systematic review. This review provides strong evidence that the pharmacological properties and different mechanisms of action of LS give it an upper hand over other inotropic agents for its successful administration in patients with either acute or advanced cardiac failure, which consists of left as well as right ventricular failure, either individually or in combination.

Propionate alleviated post-infarction cardiac dysfunction by macrophage polarization in a rat model

The propionate (C3), the important components of short-chain fatty acids (SCFAs), had the effect of inhibiting pro-inflammatory macrophages. Earlier macrophages phenotypic transition from pro-inflammatory M1 to reparative M2 in early stage was a central juncture of cardiac dysfunction mitigation after myocardial infarction (MI). 160 Sprague-Dawley rats were assigned to 4 groups: sham group (n=40), sham+C3 group (n=40), MI group (n=40) and MI+C3 group (n=40). The rats in sham+C3 and MI+C3 group were treated with oral sodium propionate (200mM), and equivalent concentration of sodium chloride was administered in sham and MI group as control. After 7days of propionate adaptive feeding, rats were anesthetized and induced the MI by coronary occlusion. The classification of macrophages, the level of inflammatory factors and inflammatory signaling were estimated at 3rd days after thoracotomy, and the extent of myocardial fibrosis was evaluated at 7th and 28th days after operation. Echocardiography was estimated on 28th day after surgery. RAW264.7 cells, stimulated by LPS+IFN-γ with or without propionate, were harvested for western blot and supernatants were collected for cytokine analysis by ELISA. Propionate administration reduced the MI-induced myocardial fibrosis in infarcted border and attenuated cardiac function deterioration compared with MI group. In comparison with MI group, propionate promoted macrophages reduction, macrophage M2-like polarization, and inflammatory cytokines decrease in infarcted border zone following MI, which partly depends on the inhibition of JNK/P38/NFκB signaling pathways. Oral propionate in early stage, as a nutritional intervention, alleviated post-MI chronic cardiac remodeling and cardiac dysfunction at least in part by modulating macrophages polarization and pro-inflammatory cytokine, which were associated with reduction of JNK/P38/NFκB phosphorylation.

Neurovascular hypoxia after mild traumatic brain injury in juvenile mice correlates with heart-brain dysfunctions in adulthood.

Retrospective studies suggest that mild traumatic brain injury (mTBI) in pediatric patients may lead to an increased risk of cardiac events. However, the exact functional and temporal dynamics and the associations between heart and brain pathophysiological trajectories are not understood. A single impact to the left somatosensory cortical area of the intact skull was performed on juvenile mice (17 days postnatal). Cerebral 3D photoacoustic imaging was used to measure the oxygen saturation (sO2 ) in the impacted area 4h after mTBI followed by 2D and 4D echocardiography at days 7, 30, 90, and 190 post-impact. At 8months, we performed a dobutamine stress test to evaluate cardiac function. Lastly, behavioral analyses were conducted 1 year after initial injury. We report a rapid and transient decrease in cerebrovascular sO2 and increased hemoglobin in the impacted left brain cortex. Cardiac analyses showed long-term diastolic dysfunction and a diminished systolic strain response under stress in the mTBI group. At the molecular level, cardiac T-p38MAPK and troponin I expression was pathologic modified post-mTBI. We found linear correlations between brain sO2 measured immediately post-mTBI and long-term cardiac strain after 8months. We report that initial cerebrovascular hypoxia and chronic cardiac dysfunction correlated with long-term behavioral changes hinting at anxiety-like and memory maladaptation. Experimental juvenile mTBI induces time-dependent cardiac dysfunction that corresponds to the initial neurovascular sO2 dip and is associated with long-term behavioral modifications. These imaging biomarkers of the heart-brain axis could be applied to improve clinical pediatric mTBI management.

Long-term Clinical Outcomes of Coronary Rotational Atherectomy for Specific Indications

Objective: This study compared the long-term outcomes between rotational atherectomy (RA) for specific indications and on-label use of RA for severely calcified coronary lesions. Methods: Data for patients who underwent RA between 2015 and 2020 in a single-center registry were analyzed. The specific indication group included patients with ostial lesions, unprotected left main coronary artery stenosis, chronic total occlusions, stent ablation, angulated lesions, and cardiac dysfunction, whereas patients with none of the above-mentioned characteristics were included in the on-label group. The primary endpoint was compared between groups. Results: A total of 176 patients in the on-label group and 125 patients in the specific indication group were included. Patient clinical characteristics were comparable between groups. The incidence of complications during the procedure was higher in the specific indication group than in the on-label group (20.0% vs. 10.8%, P=0.018). No significant difference was observed in in-hospital MACCE between groups (12.5% vs 9.7%, P=0.392). During 35 (10–57) months of follow-up, MACCE occurred in 46 patients (15.3%). The incidence of MACCE was much higher in the specific indication group than the on-label group (25.6% vs 13.6%, P=0.034). Conclusions: RA for specific indications, compared with on-label use, had a higher incidence of complications during the procedure and poorer long-term clinical outcomes.

Dietary choline, via gut microbe- generated trimethylamine-N- oxide, aggravates chronic kidney disease-induced cardiac dysfunction by inhibiting hypoxia-induced factor 1α.

Chronic kidney disease (CKD) is a global public health problem that shortens lifespan primarily by increasing the risk of cardiovascular diseases. Trimethylamine-N-oxide (TMAO), a gut microbiota-derived toxin produced by metabolizing high-choline or carnitine foods, is associated with cardiovascular events in patients with CKD. Although the deleterious effect of TMAO on CKD-induced cardiac injury has been confirmed by various researches, the mechanisms remain unclear. Here, we tested the hypothesis that TMAO aggravates CKD-induced cardiac injury and explores the potential mechanism. CD1 mice underwent 5/6 nephrectomy to induce CKD, and then fed with a diet supplemented with choline (1.2% total) for 8weeks. Serum TMAO levels were elevated in CKD mice compared with SHAM group, and higher TMAO levels were found in choline-supplemented CKD mice compared with CKD group. Dietary choline aggravated CKD-induced cardiac dysfunction, and reducing TMAO levels via medicinal charcoal tablets improved cardiac dysfunction. RNA-seq analysis revealed that dietary choline affected cardiac angiogenesis in CKD mice. Reduced cardiac capillary density and expressions of angiogenesis-related genes were observed in choline-treated CKD mice. Furthermore, dietary choline inhibited cardiac Hif-1α protein level in CKD mice, and Hif-1α stabilizer FG-4592 could improve cardiac angiogenesis and dysfunction in CKD mice on a high-choline diet. In conclusion, these data indicate that dietary choline, via gut microbe-generated TMAO, inhibits cardiac angiogenesis by reducing Hif-1α protein level, ultimately aggravates cardiac dysfunction in CKD mice.

Comparative evaluation of cardiac health in patients with chronic liver disease secondary to HCV, HBV, and NASH

Background: There is a documented relationship between chronic liver disease and cardiac dysfunction. The current investigation aims to compare the cardiac health in patients with chronic liver disease secondary to HCV, HBV, and NASH. Patients and Methods: This prospective study included 150 patients divided into three groups; Group I (50 HCV cases), Group II (50 HBV cases), and Group III (50 NASH cases). Each group was subdivided into two equal subgroups; the A subgroup included patients without liver cirrhosis, and the B subgroup included patients with liver cirrhosis. The assessment included laboratory biomarkers, transabdominal ultrasound, fibroscan, echocardiography, and carotid doppler. Results: EF had mean values of 62.58, 62.8, and 64.14%, whereas prolonged QT interval was noted in 30%, 40%, and 37% of patients in the three groups, respectively. E/A ratios > 1 were detected in 70%, 66%, and 72% of patients, while carotid atherosclerosis was detected in 28%, 28%, and 32% in the same three groups, respectively. All of the previous parameters were comparable between the three main groups. On comparing subgroups A to B, prolonged QT intervals, carotid atherosclerosis, and decreased EF were more noticed in the latter.

Cardiac functional status of patients with Chronic Kidney Disease: A cross sectional study

Background: In the recent years, the prevalence of chronic kidney disease (CKD) has increased in the community. CKD has been associated with several cardiac diseases. The aim of the study was to assess the cardiac status of the CKD patients. Methods: This cross-sectional study was done in Rangpur Medical College Hospital, Rangpur from June 2013 to November 2013. A total of 50 CKD patients were selected by convenient type of sampling. An informed written consent was taken before enrolling the patients into the study. All the data were recorded in a pre-structured questionnaire. Analysis of the data was done by SPSS V.22. A P value of <0.05 was considered as significant. Results: A total of 50 cases were studied; age ranging from 23 years to 75 years and the mean age ± SD was 45.8 ± 11.56. We study showed that 30% of patients had cardiac dysfunction, among them 18% had systolic dysfunction and 12% had diastolic dysfunction. In the study, among the diastolic dysfunction 10% had slow relaxation pattern and 02% had restrictive pattern of diastolic dysfunction. In our study, we have seen that 36% patients had left ventricular hypertrophy. ECG findings showed that 36% of patients had LVH, 6% showed anterolateral ischaemia, 6% showed inferior ischaemia, 4% showed sinus bradycardia, 2% sinus tachycardia, 2% anterior ischaemia and 2% septal ischaemia. In our study chest X-ray P/A view showed 30% had cardiomegaly, 4% had pulmonary oedema, 4% had pleural effusion and 62% had normal findings. When we staged the CKD with the GFR, it was shown that 90% patients had GFR <15, 6% had GFR in between 30—59 and 4% had in between 15-29ml/min. Systolic dysfunction was more (8%) in patients having GFR < 15, whereas it was only 1% in patients having GFR in between 30—59. Conclusion: This study an suggested association between chronic kidney disease (CKD) and cardiac dysfunction, both systolic and diastolic. It demonstrated a high prevalence left ventricular hypertrophy (LVH) as well. Early detection and treatment of causes of CKD should be pursued aggressively at the earliest possible time to prevent cardiovascular complications and thus reduce morbidity. Bangladesh Crit Care J September 2022; 10(2): 99-103