A world-first study at Oxford's John Radcliffe Hospital is seeking to answer the "obesity paradox" of the link between being overweight and heart function.
Doctors are seeking volunteers to examine why studies suggest overweight people with heart failure may live longer than sufferers who are not overweight.
Although being overweight is more likely to lead to heart failure, this "paradox" between sufferers of different weights is little understood.
People of healthy weight and overweight people with and without heart disease are being sought for the study, being run by the University of Oxford and Oxford University Hospitals NHS Trust.
One group of overweight volunteers with or without heart failure will be supported in losing a significant amount of weight.
Using scans, blood tests and exercise tests, researchers hope to better understand the impact of weight loss on heart muscle among overweight people.
It hopes to understand if there are differences in heart energy levels and pumping function in overweight people with heart failure compared to those of normal weight.
It also aims to understand if overweight people with heart failure get the same benefits from losing weight as overweight people without heart failure.
These benefits include the impact on high blood pressure, diabetes and symptoms such as breathlessness.
This will be the first time that the impact of weight loss on heart function has been assessed in this way and will use cutting edge imaging techniques which are used in only one other centre in the world, Johns Hopkins University in the United States.
It will use cardiac magnetic resonance imaging (MRI) and echocardiography (ultrasound gel scans) to take images of the heart muscle, measuring accurately its thickness and strength.
The study will also use a special MRI technique called magnetic resonance spectroscopy (MRS) to measure how efficiently heart muscle cells are using energy to assess whether this is linked to symptoms of breathlessness during exercise, a fitness bike and walk test.
Volunteers must be aged 18 to 85 and will attend two sessions of about three hours, with a repeat visit after 12 months.
Researchers are seeking 20 people with no heart problems with a Body Mass Index (BMI) up to 25; 20 people with heart failure with a BMI up to 25; 20 people with no heart problems with a BMI up to 30 and 40 people with heart failure and a BMI up to 30.
The study is being funded by the British Heart Foundation (BHF).
University of Oxford lead researcher Dr Oliver Rider said: "Obesity is already a worldwide epidemic with over 300 million people affected, and if a person has been obese for 20 years, there is a 70 per cent chance of them developing heart failure.
"However, once they have developed the disease, their prognosis is better than people of normal weight - this 'paradox' has yet to be explained.
"We want to investigate the relationship between body weight and heart function in more detail, and in particular the impact of intentional weight loss as this has never been studied in this patient group. We are interested in the effects of weight loss on heart energy use and patient symptoms, and also hope to see improvements in heart strength."
Professor Jeremy Pearson, Associate Medical Director at the BHF, said: "People who are overweight are more likely to have high blood cholesterol, high blood pressure and a higher chance of developing Type 2 diabetes, all which contribute to the development of heart disease.
"However, paradoxically, research has shown that overweight people suffering from heart failure often live longer than those who are healthy weight. Understanding why this is the case, and the effects of losing weight on the heart, could help improve advice given to heart failure patients. By supporting the research programme, you could help us find new ways of combatting heart failure, whilst taking part in a supported weight-loss programme."
Among those who is taking part is Valerie Oliver, 70, of Kingham, West Oxfordshire.
While Valerie, who weighs 13st3lbs, does not have heart failure, she chose to take part after suffering chest pains.
Now she is trying to lose weight using a traffic light food system provided by researchers which has so far included cutting down on fatty foods and cutting her portions.
She said: "I thought it will help me find out what the problem is, that was my motivation to start with. I used to do a lot of exercise but I had a knee operation so I can't do much now so I thought I'd go for this.
"I think more people should join in the research programme as heart disease is a big problem. It is very safe, they look after you."
People can find out how to take part in the study by contacting Dr Jenny Rayner on 01865 234591 or 07713 782193, or email jenny.rayner@cardiov.ox.ac.uk.