Tag: myocardial infarction

Categories : Cardiovascular Disease New Compounds and TreatmentsTags :

Averting Heart Failure by Shutting Down a Heart Protein

On By ModernMedia
Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

Shutting down a protein found in cardiac muscle could be a new mechanism to treat post-heart attack heart failure, according to research led by the University of Cambridge.

New drugs are needed to improve the heart’s pumping ability after damage from a heart attack. Drugs that strengthen the contraction of failing heart muscle have been deemed unsafe, leaving a gap in the heart attack and heart failure armamentarium.

Researchers now believe that they might have identified a new drug target—a protein called MARK4.

In research funded by the British Heart Foundation (BHF), Cambridge scientists found levels of MARK4 were elevated in mouse hearts after a heart attack. When they compared mice with and without MARK4 in the heart, they found hearts lacking the protein pumped blood 57% more efficiently. This protective effect was seen 24 hours after a heart attack and persisted over the entire follow-up period of four weeks.

The team was first in identifying that MARK4 fine-tunes a structural network within the heart muscle cell—called the microtubule network—that attaches to the machinery governing heart muscle cells contraction and relaxation. When MARK4 levels were increased after a heart attack, microtubules were tightly anchored onto the contractile machinery in the heart, increasing resistance and hindering normal function. When MARK4 levels were reduced, microtubules were loosely anchored, making contraction and relaxation easier.

Following a heart attack the speed of contraction in MARK4-lacking muscle cells increased by 42 percent and the speed of relaxation increased by 47 percent, compared to muscle cells from mice that had the MARK4 protein. They were also almost on par with healthy heart muscle performance, attesting to the power of reducing MARK4.

Based on these findings, the researchers suggested that drugs to switch off MARK4 could be a new way to improve recovery and help the heart to pump blood more efficiently in people with failing hearts.

Dr Xuan Li, BHF Intermediate Research Fellow at University of Cambridge BHF Centre of Research Excellence, said: “After years of research we’ve revealed an entirely new and promising way that could help the recovery of failing hearts.

“It’s early days, and we now need to test the longer-term effects of switching off MARK4. But if drugs to do that prove successful, the life-changing benefits could be seen in people with other types of heart disease as well as those who’ve had a heart attack and developed heart failure.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, said: “Heart attacks are a major cause of disability worldwide—people who’ve had a major heart attack are at much greater risk of developing chronic heart failure. There are around 920 000 people living with heart failure in the UK, and we desperately need drugs to drastically improve the heart’s function in these patients.

“These findings are a positive step forward. Further research is needed to refine and test drugs that can target MARK4 before we’ll see them given to people who’ve had a heart attack and develop heart failure.”

Source: University of Cambridge

Categories : Cardiovascular Disease Medical Research & TechnologyTags :

Manganese Sharpens MRI Scans of Heart Attacks

On By ModernMedia
Clinician prepares an MRI scanner. Image by Michal Jarmoluk from Pixabay

Manganese, a common trace mineral, could improve MRI scans of hearts after a heart attack and guide therapy, according to a new study.

By far the most widely used contrast agent for MRI is gadolinium, which improves the visibility of different organs and tissue types in MRI scans. However, it is taken up equally by cells regardless of their activity, and spreads out in damaged tissue. Furthermore, there are also extremely rare instances of serious kidney damage from its use. 

Manganese, besides being less toxic, has a useful property in that it competes with calcium uptake. Calcium handling is highly sensitive to altered heart muscle viability and changes rapidly after damage. Manganese ions enter heart muscle cells through calcium channels, and thus give a useful surrogate for heart tissue viability.

The contrast agent was tested first in vitro with heart muscle cells, and then in mice which had a myocardial infarction (heart attack) induced. The manganese contrast agent was administered with a calcium supplement or administered slowly to negate the effects of manganese interfering with the heart’s calcium channel. Findings were evaluated by examining the infarct size and blood supply at three key intervals: one hour, one day and 14 days after a myocardial infarction was induced. Overall, the manganese contrast agent was superior to gadolinium.

These findings could have major implications for heart attack treatment, if confirmed. They could also be greatly useful in preclinical evaluation of treatments for patients with cardiac ischaemia – where blood supply to the heart muscle is reduced, possibly leading to cardiac arrest.

Furthermore, if manganese-enhanced MRI is performed within the first few hours of a heart attack it could be used to determine the optimal treatment regime for individual patients – helping to regulate changes in the cardiac muscle and thereby further improving survival chances. 

“Magnetic resonance imaging (MRI) is increasingly used to diagnose and give information on heart conditions,” said lead researcher Dr Patrizia Camelliti, Senior Lecturer in Cardiovascular Science, University of Surrey. “This research using mice allows us to measure the health status of the heart muscle rapidly after a heart attack and could provide important information for optimizing treatments in patients.”

Source: News-Medical.Net

Journal reference: Jasmin, N.H., et al. (2021) Myocardial Viability Imaging using Manganese‐Enhanced MRI in the First Hours after Myocardial Infarction. Advanced Science. doi.org/10.1002/advs.202003987.

Categories : Cardiovascular DiseaseTags :

Recurrence Risk of Heart Attack is Increased by Long Hours

On By ModernMedia
Photo of neon-lit heart by Leon Collett, via Unsplash.

For heart attack survivors, the risk of recurrent coronary heart disease is increased by working long hours.

Heart attack survivors who working 55+ hours per week were at higher risk of recurrent coronary heart disease (CHD) events (ie, myocardial infarction [MI] or unstable angina) over 6 years compared with people working a more standard 35-40 hours a week (adjusted HR 1.67). This included adjustment for sociodemographics, lifestyle-related risk factors, clinical risk factors, work environment factors, and personality factors.

“These results showed a linear risk increase after 40 h/week and a stronger effect after the first 4 years of follow-up and when long working hours are combined with job strain,” wrote Xavier Trudel, PhD, of CHU de Québec-Laval University Research Centre in Quebec City, and colleagues. 
The researchers suggested secondary interventions in curbing working hours among patients at risk of CHD recurrence.

In an accompanying editorial, Jian Li, MD, PhD, of UCLA, and Johannes Siegrist, PhD, of Heinrich-Heine-University, concurred: A “short standardized assessment of working time and stressful working conditions among economically active cardiac patients would enrich physicians’ awareness of patients’ needs and inform medical decision making.”

“With the transformation of the modern work due to technological advances and economic globalisation, an increase in work load and an extension of irregular, nonstandard forms of employment, including working from home, were reported, aggravating the control and prevention of long working hours,” Drs Li and Siegrist wrote.

They urged cardiac rehabilitation programmes to offer “training skills of coping with stressful demands and of strengthening resilience and relaxation” and involving occupational health services to develop return-to-work plans.

When cardiac disease patients return to work, their workplaces will need to adopt tailored, programs to retain the workers and manage disease, Drs Li and Siegrist added.

The prospective cohort study included 967 MI survivors under age 60, of whom 205 had a recurrent CHD event over follow-up averaging 5.9 years.Men and people in their 40s and 50s were most likely to be working long hours after an MI. Job strain, defined as a combination of high psychological demands and low decision latitude at work, was measured with a questionnaire.

Work hours for each participant were assessed only once, at about 6 weeks after returning to work. “Some patients could have changed exposure during follow-up, leading to potential nondifferential misclassification and to an underestimation of the true effect,” Trudel’s group acknowledged.

The observational study was limited by only one tenth of participants being women, limiting generalisability, and by unknown confounding variables.

“In conclusion, the study by Trudel et al. provides a new piece of research evidence that work-related factors play an important role in CHD prognosis,” Drs Li and Siegrist wrote. “Occupational health services are urgently needed to be incorporated into cardiac rehabilitation programs and secondary prevention of CHD.”

Source: MedPage Today

Journal article information: Trudel X, et al “Long working hours and risk of recurrent coronary events” J Am Coll Cardiol 2021; DOI: 10.1016/j.jacc.2021.02.012.

Editorial information: Li J, Siegrist J “Occupational risks of recurrent coronary heart disease” J Am Coll Cardiol 2021; DOI: 10.1016/j.jacc.2021.02.020.