Cardiotonic Agent Research Articles

Levosimendan in pediatric and neonatal practice – Pro and Contra

The problem of intensive shock therapy of various etiologies in neonatology remains relevant. Anatomical and physiological features of the cardiovascular system and changes that occur during the first weeks of life in children affect the choice and dose of drugs to resolve a critical condition. The shortcomings of medications available in neonatology for the correction of arterial hypotension and shock led to the search for new drugs for the treatment of such patients.Levosimendan is a cardiotonic agent that increases the sensitivity of the heart to calcium, has a positive inotropic and vasodilatory effect, reducing preload and postload of the heart. Levosimendan has been used in neonatal practice for more than 15 years, but the lack of major studies to date evaluating its effectiveness and safety in newborns significantly limits its use. Several studies have demonstrated a positive effect of the drug on cerebral, systemic perfusion and oxygenation in newborns with low cardiac output syndrome, safety, low frequency of side effects and reduced time spent in the intensive care unit for newborns after correction of heart defects and in newborns who have suffered asphyxia. However, most of the published results of the clinical use of levosimendan in neonatology are limited to a few observations or poor quality of the study design.The available literature data indicate a good potential of the drug as a means of inotropic support, however, there is no convincing data on the effect of levosimendan on the survival of newborns in critical condition.

Antitumor effects and potential mechanisms of aconitine based on preclinical studies: an updated systematic review and meta-analysis.

Background: Herbs originating from the Aconitum L. (Ranunculaceae), such as Aconitum carmichaelii Debeaux. (Wutou), Aconitum pendulum Busch. (Tiebangchui), and Aconitum kusnezoffii Reichb. (Caowu), etc. are highly valued for their medicinal properties. The roots and tubers of these herbs are commonly used to treat an array of ailments, including joint pain and tumors. The alkaloids present in them are the primary active components, with aconitine being the most notable. Aconitine has gained attention for its exceptional anti-inflammatory and analgesic properties, as well as its potential as an anti-tumor and cardiotonic agent. However, the exact process through which aconitine hinders the growth of cancerous cells and triggers their programmed cell death remains unclear. Therefore, we have undertaken a comprehensive systematic review and meta-analysis of the current research on the potential antitumor properties of aconitine. Methods: We conducted a thorough search of relevant preclinical studies in databases including PubMed, Web of Science, VIP, WanFang Data, CNKI, Embase, Cochrane Library, and National Center for Biotechnology Information (NCBI). The search was conducted up until 15 September 2022, and the data were statistically analyzed using RevMan 5.4 software. The number of tumor cell value-added, tumor cell apoptosis rate, thymus index (TI), and Bcl-2 gene expression level were the main indicators to be analyzed. Results: After applying the final inclusion criteria, a total of thirty-seven studies, comprising both in vivo and in vitro research were analyzed. The results showed that treatment with aconitine led to a significant reduction in tumor cell proliferation, a noteworthy increase in the rate of apoptosis among tumor cells, a decrease in the thymus index, and a reduction in the expression level of Bcl-2. These results suggested that aconitine could inhibit the proliferation, invasion, and migration abilities of tumor cells by regulating Bcl-2 etc., thereby enhancing the anti-tumor effects. Conclusion: In summary, our present study demonstrated that aconitine effectively reduced tumor size and volume, indicating a strong anti-tumor effect. Additionally, aconitine could increase the expression levels of caspase-3, Bax and other targets. Mechanistically, it may regulate the expression levels of Bax and Bcl-2 through the NF-κB signaling pathway, ultimately inhibiting tumor cell proliferation through autophagy.

Levosimendan Reverses Cardiac Malfunction and Cardiomyocyte Ferroptosis During Heart Failure with Preserved Ejection Fraction via Connexin 43 Signaling Activation.

In recent decades, the occurrence of heart failure with preserved ejection fraction (HFpEF) has outweighed that of heart failure with reduced ejection fraction by degrees, but few drugs have been demonstrated to improve long-term clinical outcomes in patients with HFpEF. Levosimendan, a calcium-sensitizing cardiotonic agent, improves decompensated heart failure clinically. However, the anti-HFpEF activities of levosimendan and underlying molecular mechanisms are unclear. In this study, a double-hit HFpEF C57BL/6N mouse model was established, and levosimendan (3 mg/kg/week) was administered to HFpEF mice aged 13 to 17 weeks. Different biological experimental techniques were used to verify the protective effects of levosimendan against HFpEF. After four weeks of drug treatment, left ventricular diastolic dysfunction, cardiac hypertrophy, pulmonary congestion, and exercise exhaustion were significantly alleviated. Junction proteins in the endothelial barrier and between cardiomyocytes were also improved by levosimendan. Among the gap junction channel proteins, connexin 43, which was especially highly expressed in cardiomyocytes, mediated mitochondrial protection. Furthermore, levosimendan reversed mitochondrial malfunction in HFpEF mice, as evidenced by increased mitofilin and decreased ROS, superoxide anion, NOX4, and cytochrome C levels. Interestingly, after levosimendan administration, myocardial tissue from HFpEF mice showed restricted ferroptosis, indicated by an increased GSH/GSSG ratio; upregulated GPX4, xCT, and FSP-1 expression; and reduced intracellular ferrous ion, MDA, and 4-HNE levels. Regular long-term levosimendan administration can benefit cardiac function in a mouse model of HFpEF with metabolic syndromes (namely, obesity and hypertension) by activating connexin 43-mediated mitochondrial protection and sequential ferroptosis inhibition in cardiomyocytes.

Molecular Engineering of Metal-Organic Layers for Sustainable Tandem and Synergistic Photocatalysis.

Metal-organic layers (MOLs), a monolayered version of metal-organic frameworks (MOFs), have recently emerged as a novel two-dimensional molecular material platform to design multifunctional catalysts. MOLs inherit the intrinsic molecular tunability of MOFs and yet have more accessible and modifiable building blocks. Here we report molecular engineering of six MOLs via modulated solvothermal synthesis between HfCl4 and three photosensitizing ligands followed by postsynthetic modification with two carboxylate-containing cobaloximes for tandem and synergistic photocatalysis. Morphological and structural characterization by transmission electron microscopy and atomic force microscopy and compositional analysis by inductively coupled plasma-mass spectrometry and nuclear magnetic resonance spectroscopy establish the MOLs as flat nanoplates with a periodic lattice structure of hexagonal symmetry. The MOLs efficiently catalyze tandem dehydrogenative coupling reactions and synergistic Heck-type coupling reactions. The most active MOL catalyst was used for the gram-scale synthesis of vesnarinone, a cardiotonic agent, in 80% yield with a turnover number of 400 and in eight consecutive reaction cycles without significant loss of activities.

Abstract 10914: Acute Heart Failure Due to Rupture of an Aortic Pseudoaneurysm Into the Right Atrium

Introduction: Rupture of an aortic aneurysm into the right atrium (RA) is extremely rare, while rupture into the thoracic cavity or pericardial sac is a common fatal complication. We describe a case of acute heart failure due to rupture of an aortic pseudoaneurysm with aorta-right atrial fistula. Case Summary: A 73-year-old man presented to the emergency department with dyspnea and abdominal distention. He had a history of ascending aortic replacement for type A aortic dissection 18 years ago. On arrival, physical examination revealed diminished breath sounds, leg edema but no cardiac murmurs. Investigations demonstrated abnormality of hepatic and kidney function, elevated BNP (490.9 pg/ml) in blood exam, and enlargement of ascending aortic aneurysm at the proximal anastomotic site with ascites/pleural effusion on computed tomography (CT), while left ventricular function was normal on transthoracic echocardiogram. We diagnosed acute heart failure with preserved ejection fraction and started to reduce fluid using diuretics. However, the response to diuretics was not good and the progression of lactic acidosis was observed regardless of using cardiotonic agent. Since it was becoming difficult to maintain systemic circulation, we performed further investigations before introducing mechanical support. The pulmonary artery catheterization revealed elevated RA pressure with wide pulse pressure (38/12 mmHg) and Oxygen step up in RA. An aortic root angiogram, contrast-enhanced CT and transesophageal echocardiogram showed a rupture of aortic pseudoaneurysm complicated with aorta-right atrial fistula (Figure). Although emergent surgery was performed, he unfortunately died the following day. Conclusions: This is a rare case of intracardiac perforation of aortic aneurysm diagnosed by various modalities. We should consider the possibility of developing shunt disease when we meet patients with rapidly progressive circulatory failure unresponsive to drugs.

The pharmacotherapeutic options in patients with catecholamine-resistant vasodilatory shock

Introduction Septic and vasoplegic shock are common types of vasodilatory shock (VS) with high mortality. After fluid resuscitation and the use of catecholamine-mediated vasopressors (CMV), vasopressin, angiotensin II, methylene blue (MB) and hydroxocobalamin can be added to maintain blood pressure. Areas covered VS treatment utilizes a phased approach with secondary vasopressors added to vasopressor agents to maintain an acceptable mean arterial pressure (MAP). This review covers additional vasopressors and adjunctive therapies used when fluid and catecholamine-mediated vasopressors fail to maintain target MAP. Expert opinion Evidence supporting additional vasopressor agents in catecholamine resistant VS is limited to case reports, series, and a few randomized control trials (RCTs) to guide recommendations. Vasopressin is the most common agent added next when MAPs are not adequately supported with CMV. VS patients failing fluids and vasopressors with cardiomyopathy may have cardiotonic agents such as dobutamine or milrinone added before or after vasopressin. Angiotensin II, another class of vasopressor is used in VS to maintain adequate MAP. MB and/or hydoxocobalamin, vitamin C, thiamine and corticosteroids are adjunctive therapies used in refractory VS. More RCTs are needed to confirm the utility of these drugs, at what doses, which combinations and in what order they should be given.

Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics.

Cardiac glycosides are natural sterols and constitute a group of secondary metabolites isolated from plants and animals. These cardiotonic agents are well recognized and accepted in the treatment of various cardiac diseases as they can increase the rate of cardiac contractions by acting on the cellular sodium potassium ATPase pump. However, a growing number of recent efforts were focused on exploring the antitumor and antiviral potential of these compounds. Several reports suggest their antitumor properties and hence, today cardiac glycosides (CG) represent the most diversified naturally derived compounds strongly recommended for the treatment of various cancers. Mutated or dysregulated transcription factors have also gained prominence as potential therapeutic targets that can be selectively targeted. Thus, we have explored the recent advances in CGs mediated cancer scope and have considered various signaling pathways, molecular aberration, transcription factors (TFs), and oncogenic genes to highlight potential therapeutic targets in cancer management.

Isolation and characterization of chemical constituents with in vitro anti-hypertensive and anthelmintic activities of Cinnamomum bejolghota (Buch.-Ham.) sweet leaves: An ethno medicinal plant of North East India

Cinnamomum bejolghota (Buch.-Ham.) Sweet is traditionally use as anthelmintic and cardiotonic agent. The objective of our current experiment is to establish the traditional claim by determining the in vitro anthelmintic and antihypertensive activity of extract and isolated compounds from the leaves of the plant. Isolation of compounds was carried out by bioassay guided method from hexane and ethanol extract. In vitro anti-hypertensive activity was carried out by angiotensin converting enzyme (ACE) inhibitory method. Anthelmintic activity was done by measuring the effect of isolated compounds on the survivability of adult nematode, egg hatching and larval development of Caenorhabditis elegans. From the plant, thirteen compounds (1-13) were characterized by using chromatography and spectroscopic methods and were tested for in vitro anthelmintic and ACE inhibitory activity. Compounds linalool (1), β-sitosterol (6), cinnamic acid (11), fridelin (12) exhibited promising ACE inhibitory activity with IC50 value of 99.02 ± 0.44, 65.87 ± 0.72, 45.36 ± 0.16 and 45.45 ± 2.31 μg/ml respectively. Further, geranial (4) exhibited the highest anthelmintic property when tested against adult C. elegans with an ED50 of 57.55 ± 4.47 µg/ml. Geranial treated eggs showed that at a concentration of 47.65 ± 1.917 µg/ml approximately 50% of the eggs did not hatch and at a concentration of 200 µg/ml compound was very effective in hindering the hatching of eggs (88.66 ± 0.67%). The larval development assay shows that at a concentration of 38.73 ± 2.57 µg/ml survival of about 50% of larvae was observed. To the best of our knowledge, this is the first report of isolation of anthelmintic and antihypertensive chemical moiety from C. bejolghota and can be developed into a novel phyto-pharmaceutical product.

Cardiac Glycosides as Immune System Modulators.

Cardiac glycosides (CGs) are natural steroid compounds occurring both in plants and animals. They are known for long as cardiotonic agents commonly used for various cardiac diseases due to inhibition of Na+/K+-ATPase (NKA) pumping activity and modulating heart muscle contractility. However, recent studies show that the portfolio of diseases potentially treatable with CGs is much broader. Currently, CGs are mostly studied as anticancer agents. Their antiproliferative properties are based on the induction of multiple signaling pathways in an NKA signalosome complex. In addition, they are strongly connected to immunogenic cell death, a complex mechanism of induction of anticancer immune response. Moreover, CGs exert various immunomodulatory effects, the foremost of which are connected with suppressing the activity of T-helper cells or modulating transcription of many immune response genes by inhibiting nuclear factor kappa B. The resulting modulations of cytokine and chemokine levels and changes in immune cell ratios could be potentially useful in treating sundry autoimmune and inflammatory diseases. This review aims to summarize current knowledge in the field of immunomodulatory properties of CGs and emphasize the large area of potential clinical use of these compounds.

Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19.

Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6, representing effective drugs. The time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs which acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI > 100), atovaquone, an anti-malarial (TI > 34), and ciclesonide, an inhalable corticosteroid (TI > 6). Furthermore, utilizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we tested combinations of remdesivir with selected drugs in Vero-E6 and Calu-3 cells, in lung organoids, and identified ciclesonide, nelfinavir, and camostat to be at least additive in vitro. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses.

3-Cyano-2-oxa-pyridines: a promising template for diverse pharmacological activities

Pyridines have occupied a unique place in medicinal chemistry as it is widely profound as natural products and formed the integral backbone of great number of drugs in the market. In particular, 3-cyano-2-oxa-pyridines showed diverse biological and pharmacological activities such as cardiotonic, antimicrobial, antidepressant, and anticancer activity. 3-Cyano-2-oxa-pyridine derivatives have elevated importance for modern medicinal applications especially in cancer therapy. This article shed light on the general chemical synthetic approaches of 3-cyano-2-oxa-pyridines and summarized their various biological activities and pharmacological uses. This article may be helpful in the future to direct attention towards utilization of 3-cyano-2-oxa-pyridine template in the design of new molecules with enhanced biological properties such as PIM1 kinase, tubulin polymerase and survivin inhibitors for cancer therapy or new AMPK activator for diabetes and obesity control or cardiotonic agents.

Biologically active substances of some species of the genus Asteraceae

Currently, 40% of drugs used in modern medicine are obtained from plant raw materials. Among the wild flora there are medicinal plant species containing a variety of chemical composition, including biologically active substances with antimicrobial activity and phytoncidal properties. This article presents biologically active substances of some species of the genus Asteraceae . The chemical composition of plants belonging to the Asteraceae family is represented by anthocyanins, inulins, pectins, flavonoids, proteins, cloves, fatty oils, coumarins, carotenes and polyphenols. The plant of the Asteraceae family is used in folk medicine as an anti-inflammatory, antitumor and cardiotonic agent.

Development of the quantitative test methods to determine the number of flavonoids in flowering shoots of semi-soft hawthorn

Flowers, fruits and shoots of various genus Hawthorn (Crataegus L.) species are used in domestic and foreign medical practice as cardiotonic agents. It is also possible to use hawthorn raw material for the prevention of cardiovascular system diseases among medical and pharmaceutical personnel. We consider semi-soft hawthorn Crataegus submollis Sarg. to be a prospective raw material species as its flowering shoots are chemically similar to the red-haw hawthorn flowers. We developed the quantitative test method to determine the number of flavonoids expressed as hyperoside in flowering shoots of semi-soft hawthorn using differential spectrophotometry with an analytical wavelength of 412 nm.

Integrated artificial neural network analysis and functional cell based affinity mass spectrometry for screening a bifunctional activator of Ca2+ and β2AR in aconite

Arrhythmia, a common heart disease, is an abnormal frequency or rhythm of heartbeat caused by the origin or conduction obstacle of the heart. Aconite (Fuzi) has been regarded as an effective cardiotonic agent in traditional Chinese medicine (TCM), but it sometimes induces cardiac toxicity, such as arrhythmia, in the clinic. It is still a challenge to identify the active ingredients related to the therapeutic effect or toxicity in the application of aconite. To clarify which ingredient or derivative plays a key role of reducing toxicity and improving efficiency in the use of aconite, a serum pharmacology approach integrated with metabolomics and artificial neural network (ANN) analysis was used to in vivo screen Ca2+ and β2AR regulators from the extracts of Heishunpian (HSP), which a processed lateral root of aconite. In addition, β2AR transfected CHO and myocardium H9C2 functional cells-based affinity mass spectrometry (AMS) screening tests were carried out for evaluating the active ingredients in vitro. The results demonstrated that the monoester diterpenoid alkaloids (MDAs) represented by fuziline were the key bifunctional activators that could activate Ca2+ and β2AR simultaneously. The effective compatibility of the calcium antagonists could regulate the heart rhythm to alleviate arrhythmia while maintain their cardiotonic effect, which was induced by aconite. In this study, ANN analysis based on serum pharmacology combined with AMS screen, which utilized with functional cells presented a powerful analytical strategy to the discovery and evaluation of active ingredients from a complex system.

Pharmacognostic and pharmacological study of liquid extract of Crataegus Submollis Sarg. Flowers

The flowers and fruits of various species of the hawthorn genus (Crataegus L.) are widely used in domestic and foreign medical practice as cardiotonic agents. A perspective species for collecting of the raw material is Crataegus submollis Sarg. It was determined that 70% ethanol is an optimal extragent for the extraction of flavonoids from Crataegus submollis Sarg. flowers. The content of the total flavonoids in terms of hyperoside in the liquid extract of Crataegus submollis Sarg. flowers is 0,24 0,01%. It was established that liquid extract of Crataegus submollis Sarg. with using of 70% ethanol in case of a single intragastric administration in the dose of 100 l/kg shows significant antidepressant activity. Crataegus submollis Sarg. flowers are the perspective medicinal plant raw materials.

Levosimendan Can Improve the Level of B-Type Natriuretic Peptide and the Left Ventricular Ejection Fraction of Patients with Advanced Heart Failure: A Meta-analysis of Randomized Controlled Trials.

Levosimendan, a calcium (Ca2+)-sensitizing cardiotonic agent, is mainly used in patients with advanced heart failure. However, no research could explain how levosimendan reduces the mortality in advanced heart failure patients. We aim to illustrate the efficacy of levosimendan through clinical indexes. We searched PubMed, Embase, and CENTRAL from 1994 to August 2019 to compare the efficacy of levosimendan infusion for the treatment of advanced heart failure with that of other agents (placebo, dobutamine, furosemide, and prostaglandin E1). Levels of B-type natriuretic peptide (BNP) and N-terminal pro BNP (NT-proBNP), and left ventricular ejection fraction (LVEF) and heart rate (HR) were analyzed. The count data were analyzed by the standardized mean difference (SMD) and its 95% confidence interval (CI) to determine the effect size. We chose the random effect model or the fixed effect model according to the heterogeneity. Nine randomized controlled trials with 413 patients were ultimately enrolled. Compared with other agents (placebo, dobutamine, furosemide, and prostaglandin E1), levosimendan significantly reduced the BNP level (SMD -0.91; 95% CI -1.44 to -0.39; p = 0.001; I2 = 74.3%) and improved the LVEF (SMD 0.74; 95% CI 0.22-1.25; p = 0.005; I2 = 79.7%). However, levosimendan did not significantly change the HR (SMD0.09; 95% CI -0.24 to 0.42; p = 0.592; I2 = 51.5%). Meanwhile, we found that the main source of heterogeneity was the use of loaded or unloaded levosimendan. Our meta-analysis suggests that intravenous levosimendan can reduce BNP level and increase LVEF in patients with advanced heart failure to reduce the mortality at the shortest follow-up available.

Ethnomedicinal Plants Used for the Treatment of Cardiovascular Diseases by Healers in the Southwestern State of Paraná, Brazil, and Their Validation Based on Scientific Pharmacological Data.

Cardiovascular diseases are responsible for high morbidity and mortality rates worldwide. Among treatment options, medicinal plants are frequently used, especially in developing countries, such as Brazil. Despite social development that has been observed in the last decades, the use of medicinal plants is still driven by popular knowledge, especially by healers. The present study sought to identify medicinal species that are used for the treatment of cardiovascular diseases by healers in the microregion of Francisco Beltrão, Paraná, Brazil. The snowball technique was used to select informants, and data were collected through interviews. The research was performed in two stages: (1) a structured interview and (2) the collection and botanical identification of the species that were mentioned by the healers. Medicinal plants were classified into the following categories of cardiovascular agents: hypotensive and antihypertensive agents, lipid-lowering agents, diuretic agents, and cardiotonic agents. To analyze the data, the frequency was determined, Spearman correlations were calculated, and the informant consensus factor (ICF) and use value were obtained. Some characteristics, such as female gender and old age, were associated with knowledge about medicinal plants. Overall, 77 different species and 149 medicinal uses were cited by the healers. With regard to categories of use, the highest number of species was found among lipid-lowering plants, and the highest ICF was found for species that are used as cardiotonics. Moreover, a literature review indicated that among the cited species, several still lack studies that have proven their effects on the cardiovascular system. The traditional use of medicinal plants for the treatment of cardiovascular diseases is broad in the study regions. The present results are important for clarifying popular knowledge in this region and providing a framework for selecting species with potential for the development of new pharmacological studies.

Cardiovascular disease in the homeless: a systematic review of observational and interventional studies

BackgroundCardiovascular disease causes excess mortality and morbidity in socially excluded (inclusion health) populations. However, no specific guidelines exist for the treatment of cardiovascular disease in these individuals, including homeless populations. We aimed to better understand the disease burden and to identify evidence-based interventions in this setting by reviewing studies examining targeted interventions and prevalence of cardiovascular disease in homeless individuals. MethodsIn this systematic review, we searched Embase for observational and interventional studies of cardiovascular disease in homeless populations published on or before Dec 19, 2018, using the keywords “heart diseases”, “adrenergic beta-antagonists”, “cardiotonic agents”, “cardiovascular diseases”, “cardio-renal syndrome”, “hypertension” and “homeless [population]”. Two independent reviewers selected eligible articles and extracted relevant data, and used the Newcastle-Ottawa Scale to grade the quality of studies. The main outcome, assessed by a random-effects meta-analysis, was prevalence of cardiovascular disease (International Classification of Diseases-10 definition). FindingsOf 273 full-text articles that were retrieved, 17 (six case-control, 11 cohort) met the inclusion criteria, none of which considered interventions for cardiovascular disease. 13 (76%) of 17 were high quality, and all were based in Europe or North America, including 765 459 individuals, of whom 32 721 were homeless. 12 (71%) of 17 studies were published before 2011. Homeless individuals were more likely to have cardiovascular disease than were non-homeless individuals (pooled odds ratio [OR] 2·96 [95% CI 2·80–3·13]; p<0·0001; pheterogeneity<0·0001). North American homeless individuals were more likely to have cardiovascular disease (pooled OR 3·07 [2·90–3·25]; p<0·0001; pheterogeneity=0·0070) than their European counterparts (pooled OR 2·15 [1·81–2·54]; p<0·0001; pheterogeneity=0·125). Compared with non-homeless individuals, hypertension was more likely in homeless people (pooled OR 1·38–1·09, 1·75; p=0·0070; heterogeneity p=0·94. InterpretationHomeless populations are at increased risk of cardiovascular disease. However, studies to-date are limited in number, geography and contemporary relevance with no interventional studies and considerable heterogeneity between existing studies. The increased burden of cardiovascular disease in homeless populations requires better characterisation and interventions need to be designed and tested urgently. Cardiovascular disease needs to be studied further in this setting if integrated care in homeless individuals is to become a reality. FundingNational Institute of Health Research Programme Development Grant (RP-DG-0117–10003).

Cardiomegaly of the larger twin in monochorionic twin pregnancies warrants neonatal intensive care even without twin-to-twin transfusion syndrome

ObjectivesSome monochorionic twin pregnancies need intensive cardiac management even in the absence of twin-to-twin transfusion syndrome after birth. The purpose of this study was to investigate risk factors related to persistent hypotension requiring cardiotonic agent use among monochorionic twin pregnancies without twin-to-twin transfusion syndrome. Study designThis was a retrospective study of 316 monochorionic twin pregnancies without twin-to-twin transfusion syndrome (632 babies). All cases were treated in the neonatal intensive care unit. Hypotension was defined as mean arterial blood pressure below the norm for gestational age. Decreased left ventricular ejection fraction was defined as a value <60%. Dopamine, dobutamine and phosphodiesterase III inhibitor were used as cardiotonic agents for hypotension persisting even after adequate infusion. ResultsAmong the 632 cases, 33 (5.2%) needed cardiotonic agents for persistent hypotension. The frequency of persistent hypotension with decreased left ventricular ejection fraction was significantly higher among larger twins (4.4%) than among smaller twins (0.6%, p = 0.0038). In larger twins, multivariate analysis showed that Z-score for cardiothoracic area ratio (odds ratio, 2.31; p < 0.001), tricuspid regurgitation (odds ratio, 6.34; p = 0.015) and gestational age at delivery (odds ratio, 0.66; p < 0.001) correlated with persistent hypotension. In smaller twins, univariate analysis showed gestational age at delivery, birth weight, Z-score for birth weight and Z-score for cardiothoracic area ratio of the larger twin were related to persistent hypotension. Concentration of brain natriuretic peptide in the umbilical vein in larger and smaller twins were significantly correlated (coefficient of correlation = 0.792, p < 0.001). ConclusionsIn monochorionic twin pregnancies, attention needs to be given to cardiac size along with amniotic fluid and fetal growth. Both larger and smaller twins carry risks of persistent hypotension after birth. Close observation is needed, especially in cases where the larger twin displays cardiomegaly despite absence of twin-to-twin transfusion syndrome.

Heart Transplantation as a Treatment Method for Refractory Heart Failure due to Post-myocarditis Dilated Cardiomyopathy: a Clinical Case

Background. Implementation of mechanical circulatory support and heart transplantation technologies in paediatric clinical practice is changing approaches of diagnostics and treatment of heart failure (HF) in children. The experience of carrying out such operations in Russian Federation is extremely limited until recently due to absence of legal mechanisms of people declaration of intention recording about postmortal use of organs for transplantation.Clinical Case Description. The rare clinical case of drug-refractory (cardiotonic agents and cardioverter defibrillator implantation) chronic cardiac failure caused by post-myocarditis dilated cardiomyopathy (DCM) which demanded heart transplantation. Postoperative course, specific and non-specific complications, diagnostics and correction approaches are described.Conclusion. In the absence of proper analysis of non-specific slight symptoms myocarditis can progress to DCM and be complicated by development of refractory HF. The only method of sustaining child’s life in such case is heart transplantation which is connected with high risk of numerous and life-threatening complications.