Search

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.

Cardiovascular complications are common in COVID-19 and strongly associated with disease severity and mortality. However, the mechanisms driving cardiac injury and failure in COVID-19 are largely unknown. We performed plasma proteomics on 80 COVID-19 patients and controls, grouped according to disease severity and cardiac involvement. Findings were validated in 305 independent COVID-19 patients and investigated in an animal model. Here we show that senescence-associated secretory proteins, markers of biological aging, strongly associate with disease severity and cardiac involvement even in age-matched cohorts. FSTL3, an indicator of Activin/TGFβ signaling, was the most significantly upregulated protein associated with the heart failure biomarker, NTproBNP (β = 0.4;padj=4.6x10− 7), while ADAMTS13, a vWF-cleaving protease whose loss-of-function causes microvascular thrombosis, was the most downregulated protein associated with myocardial injury (β=-0.4;padj=8x10− 7). Mendelian randomization supported a causal role for ADAMTS13 in myocardial injury. These data provide important new insights into the pathophysiology of COVID-19 cardiovascular complications with therapeutic implications.

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.

Rationale: Pathological hypertrophy commonly leads to heart failure (HF) and loss of cardiomyocytes, while physiological hypertrophy protects the heart and enhances cardiomyogenesis. The mechanisms underlying these differences remain unclear. While long noncoding RNAs (lncRNAs) are important in cardiac development and disease, their role in physiological hypertrophy is unknown. Objective: To investigate the role of lncRNAs in physiological hypertrophy. Methods and Results: Mice underwent voluntary wheel running for eight weeks or transverse aortic constriction (TAC) for two or ten weeks. RNAseq identified a novel set of lncRNAs altered in exercised hearts, which we termed l ong n on c oding Ex ercise- A ssociated C ardiac T ranscripts (lncExACTs). lncExACT1 was highly conserved and uniquely downregulated in exercised hearts but upregulated in pathological animal models and hearts from HF patients vs controls (1.8-fold; p p =0.032, N=16) and preserved ejection fraction (3.4-fold; p =0.006, N=18). In mice, AAV9 lncExACT1 overexpression increased cardiac lncExACT1 7-fold at 16 weeks and increased heart (HW) and lung (LW) weight relative to tibial length (TL), reduced fractional shortening (FS) and increased relative wall thickness (RWT) ( p p p Conclusions: lncExACT1 acts as a master switch toggling the heart between physiological and pathological growth and provides a potentially tractable therapeutic target for harnessing the beneficial effects of exercise.