Age-dependent Lamin remodeling induces cardiac dysfunction via dysregulation of cardiac transcriptional programs

As we age, structural changes contribute to progressive decline in organ function, which in the heart acts through poorly characterized mechanisms. Utilizing the rapidly aging fruit fly model with its significant homology to the human cardiac proteome, we found that cardiomyocytes exhibit progressive loss of Lamin C (mammalian Lamin A/C homologue) with age. Unlike other tissues and laminopathies, we observe decreasing nuclear size, while nuclear stiffness increases. Premature genetic reduction of Lamin C phenocopies aging’s effects on the nucleus, and subsequently decreases heart contractility and sarcomere organization. Surprisingly, Lamin C reduction downregulates myogenic transcription factors and cytoskeletal regulators, possibly via reduced chromatin accessibility. Subsequently, we find an adult-specific role for cardiac transcription factors and show that maintenance of Lamin C sustains their expression and prevents age-dependent cardiac decline. Our findings are conserved in aged non-human primates and mice, demonstrating age-dependent nuclear remodeling is a major mechanism contributing to cardiac dysfunction.

A successful placement of the left ventricular lead for the cardiac resynchronization device using the orthodromic snare technique: clinical case

Background: The main aim of Cardiac Resynchronization Therapy (CRT) is a positive response of the patient, particularly, reduction of the symptoms and improvement of the heart contractility, that can be reached in 5070% of patients. The possibility of appropriate positioning the left ventricular (LV) lead is of great importance for the response to CRT. Certain instruments and technical approaches are used for the placement of the LV lead. Here, we describe the use of the orthodromic snare technique, which is quite rare in practice, but allows one to overcome some anatomical obstacles. Clinical case description: Patient A., suffering from the heart failure with a low ejection fraction and left bundle branch block, was admitted to the hospital for CRT implantation. Before the operation, all the necessary routine instrumental and laboratory diagnostics was performed. During the operation, venography of the cardiac veins revealed unsuitability of the lateral cardiac vein for the placement of the LV lead due to its very small diameter. The posterolateral vein was suitable for the LV lead implantation but still had some anatomical difficulties: an acute angle of inflow and local stenosis in the proximal segment. During the procedure, the following techniques were used without success: positioning the LV lead by a simple translational movement forward, a subselective catheter, introduction of several coronary guides in order to smooth out the acute angle of inflow. These circumstances warranted the use of the orthodromic snare technique for a successful LV lead placement. Conclusion: This clinical case illustrates the possibility of a safe and effective use of the orthodromic snare technique for LV lead implantation. Such anatomical difficulties as a small diameter, acute angle of inflow, local stenosis have also been illustrated and discussed.

Cardiomyocyte Proliferation as a Source of New Myocyte Development in the Adult Heart

Cardiac diseases such as myocardial infarction (MI) can lead to adverse remodeling and impaired contractility of the heart due to widespread cardiomyocyte death in the damaged area. Current therapies focus on improving heart contractility and minimizing fibrosis with modest cardiac regeneration, but MI patients can still progress to heart failure (HF). There is a dire need for clinical therapies that can replace the lost myocardium, specifically by the induction of new myocyte formation from pre-existing cardiomyocytes. Many studies have shown terminally differentiated myocytes can re-enter the cell cycle and divide through manipulations of the cardiomyocyte cell cycle, signaling pathways, endogenous genes, and environmental factors. However, these approaches result in minimal myocyte renewal or cardiomegaly due to hyperactivation of cardiomyocyte proliferation. Finding the optimal treatment that will replenish cardiomyocyte numbers without causing tumorigenesis is a major challenge in the field. Another controversy is the inability to clearly define cardiomyocyte division versus myocyte DNA synthesis due to limited methods. In this review, we discuss several studies that induced cardiomyocyte cell cycle re-entry after cardiac injury, highlight whether cardiomyocytes completed cytokinesis, and address both limitations and methodological advances made to identify new myocyte formation.

Possibilities of Evaluating the Dynamics of Left Ventricular Perfusion and Contractility in Patients with Chronic Heart Failure after Implantation of a Heart Contractility Modulator Using Perfusion Single-Photon Emission Computed Tomography

Perfusion scintigraphy and single-photon emission tomography of the myocardium are promising methods for complex assessment of the state of the left ventricle myocardium in patients with chronic heart failure. These methods of nuclear cardiology can be performed in patients with reduced renal function, as well as the presence of implanted devices such as implantable cardioverters-defibrillators, resynchronizing devices and cardiac modulating therapy, which is their undeniable advantage. The reproducibility of the method is ensured bu fully automated calculation of parameters of myocardial perfusion and contractility. To date, there are no data in the literature on the use of nuclear cardiology methods as an imaging technique in patients with cardiac contractility modulation devises. This paper describes the current possibilities and prospects of nuclear medicine methods in patients with chronic heart failure after implantation of a heart contractility modulator.

The impact of mobilization protocols on the length of postoperative hospitalization among cardiac surgery patients

The aim. To determine the impact of implementing the extra early mobilization protocol (EEM) on the length of intensive care unit (LICU) stay and postoperative unit (LPOU) stay and to assess the role of age, heart contractility, functional class and surgical outcomes. Materials and methods. Participants – adult patients of 2018–2019 with less than 24-hour artificial lung ventilation (ALV). The first group were treated according to the early mobilization protocol (EM, patients of 2018); the second group were treated according to the EEM protocol (patients of 2019). Design: a retrospective analysis. Settings: cardiosurgical unit. Interventions: the major difference is that the resources of patient mobilization team have expanded since 2019, namely it included a physical therapist, which made it possible to modify the EM protocol (standing on the 2 postoperative day (POD), activation with the help of medical staff, respiratory exercise) to the EEM protocol (standing on the 1 POD following consultation with an anesthesiologist, exercises with a physical therapist, respiratory exercise). The main outcomes: LICU, LPOU and total postoperative hospitalization (LTPO) (number of nights). Results. There were no differences between the EEM and EM groups in LICU (3 (2; 4) vs. 2 (2; 4); P = 0.182), LPOU (7 (6; 10) vs. 8 (6; 10); P = 0.118), LTPO (10 (8; 13) vs. 10 (9; 13); P = 0.308). Correlation analysis revealed absence, weak and very weak relations between the LICU, LPOU, LTPO indicators and other criteria, including age, ejection fraction, ALV. Conclusions. The effectiveness of the EEM protocol seems doubtful to reduce LICU, LPOU, and LTPO as compared to the EM protocol. The obtained results also raise the importance of physical therapist time management.

Upregulated Angiogenesis Is Incompetent to Rescue Dilated Cardiomyopathy Phenotype in Mice

Dilated cardiomyopathy (DCM) is characterized by pathologic cardiac remodeling resulting in chambers enlargement and impaired heart contractility. Previous reports and our in-silico analysis support the association of DCM phenotype and impaired tissue angiogenesis. Here, we explored whether the modulation in cardiac angiogenesis partly intervenes or rescues the DCM phenotype in mice. Here, a DCM mouse model [α-tropomyosin 54 (α-TM54) mutant] was crossbred with microRNA-210 transgenic mice (210-TG) to develop microRNA-210 (miR-210) overexpressing α-TM54 mutant mice (TMx210). Contrary to wild-type (WT) and 210-TG mice, a significant increase in heart weight to body weight ratio in aged mixed-gender TMx210 and DCM mice was recorded. Histopathological analysis revealed signs of pathological cardiac remodeling such as myocardial disarray, myofibrillar loss, and interstitial fibrosis in DCM and TMx210 mice. Contrary to WT and DCM, a significant increase in angiogenic potential was observed in TMx210 and 210-TG mice hearts which is reflected by higher blood vessel density and upregulated proangiogenic vascular endothelial growth factor-A. The echocardiographic assessment showed comparable cardiac dysfunction in DCM and TMx210 mice as compared to WT and 210-TG. Overall, the present study concludes that miR-210 mediated upregulated angiogenesis is not sufficient to rescue the DCM phenotype in mice.

EXPERIENCE OF LEVOSIMENDAN USING IN YOUNG CHILDREN WITH FUNCTIONAL CLASS IV HEART FAILURE

Objective of the research: to study the results of levosimendan use in young children with heart failure (HF) of functional class IV (FC). Materials and methods: the analysis of observation of patients who received levosimendan: 2 with cardiomyopathies (CMP), 12 with congenital heart defects (CHD). The drug was administered intravenously 0,2 μg/kg/min. Results: in patients with CMP, the ejection fraction doubled after administration of levosimendan, in children with CHD heart contractility increased by 18%, and pulmonary artery pressure decreased by 17 mm Hg. There were no undesirable effects. Conclusion: administration of levosimendan provides an increase in cardiac output and a decrease in pulmonary resistance in children with HF IV FC without undesirable effects.

A Significant Pericardial Effusion Leading to Bronchial Compression: A Case Report

Commonly, pericardial effusions can cause suboptimal heart contractility. Larger pericardial effusions can lead to compression of structures that surround in the heart in the mediastinum. Our patient presented with dyspnea that required mechanical ventilation. Bronchoscopy revealed compression of the bronchus from an external source. Echocardiogram showed a large circumferential pericardial effusion, which compressed the left main stem bronchus causing left lung atelectasis and persistent respiratory failure. A subxiphoid pericardial window was performed, which led to an improvement in her oxygen requirements. This case portrays the importance of including pericardial effusions in patients who present with respiratory failure refractory to antibiotic treatment and intervention with bronchoscopy. Although our patient passed away, recognition and earlier appropriate management with a pericardial window or pericardiocentesis could have prevented this adverse event.

New approaches to assessing the contractile function of the left ventricular in patients with heart failure on the background of modulation of cardiac contractility.

Обзор посвящен роли современной трансторакальной эхокардиографии и новому способу неинвазивной оценки сократительной функции левого желудочка – исследованию эффективности миокардиальной работы у пациентов хронической сердечной недостаточностью. Освещаются актуальные аспекты ремоделирования левого желудочка и левого предсердия у данной категории пациентов. Обсуждается роль и важность метода спекл-трекинг эхокардиографии в оценке механической функции левого предсердия. Представлены сведения об относительно новом электрофизиологическом методе лечения - модуляции сердечной сократимости у пациентов с хронической сердечной недостаточностью, как с фибрилляцией предсердий, так и без нее. Анализируются результаты обратного ремоделирования левого желудочка по данным эхокардиографических параметров основных исследований, посвященных модуляции сердечной сократимости. В статье оцениваются перспективы применения метода оценки эффективности миокардиальной работы левого желудочка как инструмента возможного обратного ремоделирования у пациентов с хронической сердечной недостаточностью и фибрилляцией предсердий на фоне модуляции сердечной сократимости The review is devoted to the role of modern transthoracic echocardiography and a new method of non-invasive assessment of left ventricular contractile function-the study of the effectiveness of myocardial work in patients with chronic heart failure. The current aspects of left ventricle and left atrium remodeling in this category of patients are highlighted. The role and importance of speckle-tracking echocardiography in evaluating the mechanical function of the left atrium is discussed. Information is provided about a relatively new electrophysiological method of treatment-modulation of heart contractility in patients with chronic heart failure, both with and without atrial fibrillation. The results of reverse remodeling of the left ventricle are analyzed according to the echocardiographic parameters of the main studies devoted to the modulation of heart contractility. The article assesses the prospects for using the method of evaluating the effectiveness of left ventricular myocardial function as a tool for possible reverse remodeling in patients with chronic heart failure and atrial fibrillation against the background of heart contractility modulation

Protective Effects of Polyphenols against Ischemia/Reperfusion Injury

Myocardial infarction (MI) is a leading cause of morbidity and mortality across the world. It manifests as an imbalance between blood demand and blood delivery in the myocardium, which leads to cardiac ischemia and myocardial necrosis. While it is not easy to identify the first pathogenic cause of MI, the consequences are characterized by ischemia, chronic inflammation, and tissue degeneration. A poor MI prognosis is associated with extensive cardiac remodeling. A loss of viable cardiomyocytes is replaced with fibrosis, which reduces heart contractility and heart function. Recent advances have given rise to the concept of natural polyphenols. These bioactive compounds have been studied for their pharmacological properties and have proven successful in the treatment of cardiovascular diseases. Studies have focused on their various bioactivities, such as their antioxidant and anti-inflammatory effects and free radical scavenging. In this review, we summarized the effects and benefits of polyphenols on the cardiovascular injury, particularly on the treatment of myocardial infarction in animal and human studies.