lncExACT1 and DCHS2 Regulate Physiological and Pathological Cardiac Growth.

BACKGROUND: The heart grows in response to pathological and physiological stimuli. The former often precedes cardiomyocyte loss and heart failure; the latter paradoxically protects the heart and enhances cardiomyogenesis. The mechanisms underlying these differences remain incompletely understood. Although long noncoding RNAs (lncRNAs) are important in cardiac development and disease, less is known about their roles in physiological hypertrophy or cardiomyogenesis. METHODS: RNA sequencing was applied to hearts from mice after 8 weeks of voluntary exercise-induced physiological hypertrophy and cardiomyogenesis or transverse aortic constriction for 2 or 8 weeks to induce pathological hypertrophy or heart failure. The top lncRNA candidate was overexpressed in hearts with adeno-associated virus vectors and inhibited with antisense locked nucleic acid-GapmeRs to examine its function. Downstream effectors were identified through promoter analyses and binding assays. The functional roles of a novel downstream effector, dachsous cadherin-related 2 (DCHS2), were examined through transgenic overexpression in zebrafish and cardiac-specific deletion in Cas9-knockin mice. RESULTS: We identified exercise-regulated cardiac lncRNAs, called lncExACTs. lncExACT1 was evolutionarily conserved and decreased in exercised hearts but increased in human and experimental heart failure. Cardiac lncExACT1 overexpression caused pathological hypertrophy and heart failure; lncExACT1 inhibition induced physiological hypertrophy and cardiomyogenesis, protecting against cardiac fibrosis and dysfunction. lncExACT1 functioned by regulating microRNA-222, calcineurin signaling, and Hippo/Yap1 signaling through DCHS2. Cardiomyocyte DCHS2 overexpression in zebrafish induced pathological hypertrophy and impaired cardiac regeneration, promoting scarring after injury. In contrast, murine DCHS2 deletion induced physiological hypertrophy and promoted cardiomyogenesis. CONCLUSIONS: These studies identify lncExACT1-DCHS2 as a novel pathway regulating cardiac hypertrophy and cardiomyogenesis. lncExACT1-DCHS2 acts as a master switch toggling the heart between physiological and pathological growth to determine functional outcomes, providing a potentially tractable therapeutic target for harnessing the beneficial effects of exercise.

Targeting Age-Related Pathways in Heart Failure.

During aging, deterioration in cardiac structure and function leads to increased susceptibility to heart failure. The need for interventions to combat this age-related cardiac decline is becoming increasingly urgent as the elderly population continues to grow. Our understanding of cardiac aging, and aging in general, is limited. However, recent studies of age-related decline and its prevention through interventions like exercise have revealed novel pathological and cardioprotective pathways. In this review, we summarize recent findings concerning the molecular mechanisms of age-related heart failure and highlight exercise as a valuable experimental platform for the discovery of much-needed novel therapeutic targets in this chronic disease.

Pathway to cardiothoracic surgery: A primer for aspiring students.

Objective: The pathway to cardiothoracic surgery is often obscure for premedical students and aspiring applicants and requires navigating various known and unknown obstacles. Recognizing the challenges encountered on the path to a career in cardiothoracic surgery in the United States, we present this guide for students interested in the field to maximize success in their premedical, preclinical, and preresidency years. Methods: This is a joint collaboration between the Thoracic Surgery Residents Association and the Thoracic Surgery Medical Student Association. Drawing from firsthand experiences and insights gathered from numerous student applicants and current surgical residents, a comprehensive guide was constructed for students from the point of undergraduate school to advanced training options, including super-fellowship training. Results: Several intricacies to cardiothoracic surgery career planning were discussed, including differences between traditional and integrated/fast-track pathways, college and medical school selection, networking, performing during clinical rotations, extracurricular and research activities, building mentorship relationships, and pursuing alternate career and advanced training opportunities. Conclusions: For premedical students and aspiring applicants, the road to cardiothoracic surgery requires meticulous planning, grit, and thoughtful dedication. This document consolidates firsthand insights and advice from numerous aspiring and matched applicants to serve as a comprehensive guide for students seeking a career in cardiovascular and thoracic surgery.

Beyond cardiomyocytes: Cellular diversity in the heart's response to exercise.

Cardiomyocytes comprise ∼70% to 85% of the total volume of the adult mammalian heart but only about 25% to 35% of its total number of cells. Advances in single cell and single nuclei RNA sequencing have greatly facilitated investigation into and increased appreciation of the potential functions of non-cardiomyocytes in the heart. While much of this work has focused on the relationship between non-cardiomyocytes, disease, and the heart's response to pathological stress, it will also be important to understand the roles that these cells play in the healthy heart, cardiac homeostasis, and the response to physiological stress such as exercise. The present review summarizes recent research highlighting dynamic changes in non-cardiomyocytes in response to the physiological stress of exercise. Of particular interest are changes in fibrotic pathways, the cardiac vasculature, and immune or inflammatory cells. In many instances, limited data are available about how specific lineages change in response to exercise or whether the changes observed are functionally important, underscoring the need for further research.

Considerations for a Holistic Model in Evaluating Medical Students for Cardiothoracic Surgical Residency.

Program directors are tasked with selecting whom they think will be the best fit for residency and the next leaders of the field. While numerical metrics have played a vital role in this process, recent changes to student evaluation are reducing the availability of these metrics. This poses unique challenges for both applicants and program directors. Here we discuss how this will likely shift the focus on other parts of the application and the consequences (good and bad) of doing so.

Modified Barbero-Marcial repair for type I truncus arteriosus in a 2.7-kg neonate.

Truncus arteriosus is a rare cardiac anomaly, accounting for less than 4% of all congenital lesions. It is the result of failed aorticopulmonary septation during the fifth week of gestation leading to a single arterial trunk overriding the interventricular septum, a single semilunar valve, and typically a large conotruncal ventricular septal defect. Several classifications exist, and it typically requires surgical repair in the neonatal period. We present a 5-day old female neonate who was diagnosed postnatally with type I truncus arteriosus in which the pulmonary arteries arose from a discrete pulmonary trunk that originated from the posterolateral aspect of the common arterial trunk. A successful repair was undertaken using a variant of the Barbero-Marcial technique.

Non-Governmental Organizations Delivering Global Cardiac Surgical Care: A Quantitative Impact Assessment.

In low- and middle-income countries (LMICs), 93% of the population lacks safe, timely, and affordable access to cardiac surgical care when needed. As countries slowly build or expand local, independent cardiac centers, non-governmental organizations (NGOs) partially bridge the gap in cardiac surgical care delivery in LMICs. However, little is known about the current scope of cardiac NGOs. Here, we perform an analysis of active NGOs involved with the delivery of cardiac surgical services in LMICs or for patients from LMICs. Cardiac surgery NGOs were identified from medical literature, established NGO databases, and Google Scholar searches. The search was performed between December 2019 and May 2020. NGOs whose websites were not updated or described missions or projects taking place no later than 2015 were considered inactive. Eighty-six NGOs are actively providing cardiac surgery services in LMICs or treating patients from LMICs. Five NGOs performed adult cardiac surgery only, 56 performed pediatric cardiac surgery only, and 25 performed both adult and pediatric cardiac surgery. NGOs originated from 23 different countries and were operational in a total of 111 countries, 96 of them being LMICs. Fifty-three NGOs reported data on annual surgical volume, of which half performed less than 50 operations per year. NGOs effectively address the burden of cardiac surgical disease in LMICs and contribute to local capacity-building. Increased, more detailed, and standardized reporting of the impact and outcomes of NGOs is necessary to better understand annual cardiac surgical volume and to support local centers working towards independent services.

Plasma Proteomics of COVID-19-Associated Cardiovascular Complications: Implications for Pathophysiology and Therapeutics.

To gain insights into the mechanisms driving cardiovascular complications in COVID-19, we performed a case-control plasma proteomics study in COVID-19 patients. Our results identify the senescence-associated secretory phenotype, a marker of biological aging, as the dominant process associated with disease severity and cardiac involvement. FSTL3, an indicator of senescence-promoting Activin/TGFß signaling, and ADAMTS13, the von Willebrand Factor-cleaving protease whose loss-of-function causes microvascular thrombosis, were among the proteins most strongly associated with myocardial stress and injury. Findings were validated in a larger COVID-19 patient cohort and the hamster COVID-19 model, providing new insights into the pathophysiology of COVID-19 cardiovascular complications with therapeutic implications.

Resection of a large left atrial myxoma combined with mitral valve repair via a vertical right axillary thoracotomy in a pediatric patient.

Cardiac myxomas are extremely rare in the pediatric population; however, if they do develop, they occur most often in the left atrium. We present a 16-year-old male who had a murmur discovered during a routine sport examination. A transthoracic echocardiogram showed a large left atrial tumor that caused severe inflow obstruction to the left ventricle and at least moderate mitral valve regurgitation. Through a minimally invasive, muscle-sparing vertical right axillary thoracotomy, he underwent complete resection of the mass, combined with posterior mitral valve annuloplasty. A histopathological examination confirmed a cardiac myxoma.

Routine intraoperative jejunostomy placement and minimally invasive oesophagectomy: an unnecessary step?†.

OBJECTIVES: Adequate nutrition is challenging after oesophagectomy. A jejunostomy is commonly placed during oesophagectomy for nutritional support. However, some patients develop jejunostomy-related complications and the benefit over oral nutrition alone is unclear. This study aims to assess jejunostomy-related complications and the impact of intraoperative jejunostomy placement on weight loss and perioperative outcomes in patients with oesophageal cancer treated with minimally invasive Ivor Lewis oesophagectomy (MIE). METHODS: From a prospectively maintained database, patients were identified who underwent MIE with gastric reconstruction. Between 2007 and 2016, a jejunostomy was routinely placed during MIE. After 2016, a jejunostomy was not utilized. Postoperative feeding was performed according to a standardized protocol and similar for both groups. The primary outcomes were jejunostomy-related complications, relative weight loss at 3 and 6 months postoperative and perioperative outcomes, including anastomotic leak, pneumonia and length of stay, respectively. RESULTS: A total of 188 patients were included, of whom 135 patients (72%) received a jejunostomy. Ten patients (7.4%) developed jejunostomy-related complications, of whom 30% developed more than 1 complication. There was no significant difference in weight loss between groups at 3 months (P = 0.73) and 6 months postoperatively (P = 0.68) and in perioperative outcomes (P-value >0.999, P = 0.591 and P = 0.513, respectively). CONCLUSIONS: The use of a routine intraoperative jejunostomy appears to be an unnecessary step in patients undergoing MIE. Intraoperative jejunostomy placement is associated with complications without improving weight loss or perioperative outcomes. Its use should be tailored to individual patient characteristics. Early oral nutrition allows patients to maintain an adequate nutritional status.