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Heart failure is an acute or chronic, long-term condition that worsens over time and affects about 64 million people worldwide.1
What is heart failure?
Heart failure is a complex syndrome which occurs when the heart cannot pump enough blood around the body.2 It is often complicated by multiple interrelated diseases ‒ so it requires a deep understanding of the potential disease drivers for every individual heart. It affects over 64 million people across the globe and is the leading cause of hospitalisation for those over the age of 65.1,3
Current heart failure treatments follow a “one-size-fits-all” approach. However, due to the wide range of mechanisms by which heart failure can occur, one size does not fit all; up to 50% of patients die within five years of diagnosis.4 That’s why our scientists are dedicated to uncovering the underlying disease biology of heart failure to identify novel disease drivers. By harnessing the power of next generation therapeutics we aim to halt and reverse disease, restore organ damage and, one day, pave the way to a cure.
What is the difference between HFpEF and HFrEF?
There are several types of heart failure often defined by left ventricular ejection fraction (LVEF), the volume fraction of blood emptied from the heart per beat, including:
- Heart failure with reduced ejection fraction (HFrEF) (LVEF less than or equal to 40%)5-7
- Heart failure with mildly reduced ejection fraction (HFmrEF) (LVEF 41-49%)5-7
- Heart failure with preserved EF (HFpEF) (LVEF greater than or equal to 50%)5-7
While patients with chronic heart failure may have similar symptoms, ultrasound scans of their heart show different types of disease. Approximately half of all patients with heart failure have HFmrEF or HFpEF, where there are currently few therapeutic options available.8
In HFrEF, the heart has impaired pumping capacity due to coronary artery disease, myocardial infarction (heart attack) or dilated cardiomyopathy and therefore pushes less oxygen-rich blood out around the body.9 In HFpEF, the heart muscle contracts normally but thickening of the muscle due microvascular dysfunction, fibrosis or even amyloid cardiomyopathy, inadequate filling of the heart.10,11
What is the difference between heart failure and a heart attack?
Heart failure and a heart attack are two distinct medical conditions that affect the heart, although they can be related to each other.
Heart failure is a chronic condition where the heart is unable to pump blood efficiently to meet the body's needs. It occurs when the heart muscles become weakened or damaged, leading to reduced blood flow. Heart failure typically develops over time and is often a result of other heart conditions, such as coronary artery disease, high blood pressure, or previous heart damage.2
A heart attack occurs when there is a sudden blockage of blood flow to a part of the heart muscle.12 This blockage is usually caused by a blood clot that forms within a coronary artery due to atherosclerosis (buildup of plaque), and when it completely blocks the blood flow, a portion of the heart muscle becomes deprived of oxygen and starts to die.12
Heart failure can be a consequence of a heart attack.2 When a heart attack occurs, the damaged area of the heart may not function properly, leading to weakened heart muscles and an increased risk of heart failure.2
Understanding heart failure in women
Heart failure tends to occur at an older age in women than men, and women are more likely to have HFpEF.13 In pre-menopausal women, the female hormone, oestrogen, offers some protection against the coronary artery disease that commonly precedes heart failure.14,15 However, there are still a lot of unknowns about heart failure in women.
After a heart attack, women are more likely than men to develop heart failure and it has been suggested that women may receive less aggressive treatment following a heart attack than men.16,13 Guideline-recommended medical therapies for heart failure are the same for women as for men.
Research focusing on better treatment for HFpEF should be particularly beneficial for women with heart failure. We hope it will also help us learn more about how the disease progresses in women, and how access to heart failure care can be optimised for these patients.
Unravelling the complexity of HFpEF and CKD
Our early clinical programmes in chronic kidney disease (CKD) and heart failure are also being designed to allow the evaluation of common disease drivers of HFpEF as a serious comorbidity. This could potentially provide new insights into how patient outcomes change in heart failure when kidney function improves and uncover new targets that may benefit patients with both HFrEF and HFpEF, and those with CKD.
By considering different common molecular mechanisms of CKD and HFpEF, our aim is to improve outcomes in patients with one specific diagnosis before comorbidities emerge. Our focus is to really understand different subpopulations of patients for these two incredibly complex diseases, so we can work towards developing the right treatment for the right patients.
Disease-causing genes for cardiomyopathy
Cardiomyopathy can lead to heart failure and uncovering genetic insights that hold a key to transforming heart disease remain a crucial part of the drug discovery process.17
Research has revealed a significant hereditary component to heart failure, and variants in the genome have been identified to play a role in the development of the disease. We know that cardiomyopathies, a heterogeneous group of heart muscle diseases that include hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and amyloidosis cardiomyopathy, are an important cause of heart failure.
Find out how we're rising to the challenge to advance novel treatment options
so people living with cardiomyopathy and heart failure can live better healthier in the below video
By exploring subtle genetic mutations, variations in gene expression and gene-environment interactions in more common forms of heart failure, there is a potential to stratify patients for clinical trials of biomarker-guided targeted treatment.
Uncovering the various types of amyloidosis
Amyloidosis is a group of complex rare diseases caused by abnormal proteins that misfold and clump together to form toxic amyloids that deposit in tissues or organs, including the heart, kidneys and peripheral nerves.18-22 The build-up of these toxic amyloids can result in significant organ damage and organ failure that can severely impact quality of life and ultimately be fatal.19,20 Signs and symptoms of amyloidosis often resemble other diseases and lead to misdiagnosis and/or delayed diagnosis and treatment, and most existing therapies focus on preventing or suppressing the formation of new toxic amyloids.23,24
Amyloidosis has varying types and severities, including light chain (AL) amyloidosis and transthyretin-mediated amyloidosis (ATTR), such as ATTR-CM, which can cause heart failure (cardiomyopathy), and ATTR-PN, which affects function of the peripheral nerves (polyneuropathy).19-22 Additionally, some patients may present as mixed phenotype and exhibit both cardiac and neurological symptoms, which may complicate diagnosis and disease management.25,26 AL amyloidosis and ATTR can lead to HFpEF; there are both hereditary (ATTRv) and non-hereditary (wild-type) forms of ATTR.18,19
By exploring diverse yet complementary mechanisms of action to stabilise, silence or deplete toxic amyloids in organs and tissues, we seek for ways to halt and reduce organ damage for as many patients as possible – regardless of disease state, stage or phenotype.
Next wave of innovative therapeutics for heart failure
Being able to precisely target the underlying molecular cause of an individual’s disease in heart failure would be a fundamental change from current clinical management paradigms which rely mainly on clinical signs and symptoms. We are collaborating with world-leading experts to build a growing understanding of the genetic drivers of heart failure. This is helping us identify novel targets and biomarkers to discover and develop precision medicine in life-threatening diseases of the heart muscle, such as ischaemic cardiomyopathy (ICM) and idiopathic dilated cardiomyopathy (IDCM) and the inherited muscle wasting condition, Duchenne muscular dystrophy (DMD).27,28
Molecular fingerprints of heart failure
Identifying molecular fingerprints of heart failure
By harnessing the power of artificial intelligence and omics analysis, our aim is to unravel the complex disease biology of heart failure at the molecular level in individual patients. We are using machine learning to analyse large quantities of gene expression data from cardiac biopsy samples and stratify patients with heart failure into novel molecular sub-classes, irrespective of their clinical signs and symptoms. We are also using gene expression data from past trials, linked with clinical data, to see whether they correspond to clinically meaningful phenotypes. Using this wealth of new information, our aim is to identify novel therapeutic targets that will form the basis of a precision medicine approach to the care of patients with different molecular signatures of heart failure.
Improving heart muscle contraction
Targeting impaired heart muscle contraction
Among the genetic drivers of the stretched and weakened heart muscle seen in dilated cardiomyopathy (DCM) is a mutation in the gene for phospholamban (PLN).29 Excessive PLN activity is linked to cellular calcium dysregulation and impaired heart muscle contraction and relaxation.30 Whilst a key target for drug discovery, the structure of the protein has proven hard to target with conventional drugs.
Research carried out in collaboration with Ionis Pharmaceuticals and global heart failure scientists at University Medical Center Groningen and Karolinska Institute, shows that antisense oligonucleotides (ASOs) can be used to deplete the formation of PLN linked to DCM.31
Encouraging preclinical results with ASOs are making this a promising precision medicine approach in cardiomyopathy and possibly other forms of heart failure.
Miniature beating hearts
Miniature beating hearts
In the development of ‘miniature organs’ to recreate the mechanical and electrical properties in a beating heart, we are working with Novoheart to use the world’s first human-specific, in vitro functional model of HFpEF. HFpEF mini-hearts could provide a powerful tool for discovery, screening and advancement to clinical trials of novel therapeutics for heart failure.
Rare genetic drivers
Learning from rare genetic drivers of heart failure
In a recent collaboration, scientists at our Centre for Genomics research identified variants in 21 different genes linked to cardiomyopathy, irrespective of whether patients had heart failure with preserved or reduced ejection fraction – the main clinical categories of the disease.32 This means that, although patients may go to their doctor with different symptoms, their underlying genetic drivers may be similar, with environment and comorbidities playing a bigger role than previously thought.
Collaborations to support heart failure innovation
We are proud to be working with healthcare professionals, patients, governments and policy makers to improve access to healthcare, remove barriers to diagnosis and optimal treatment, changing how cardiovascular, renal and metabolic (CVRM) diseases are detected, diagnosed and treated to accelerate medical practice change together to make a difference for patients.
ACT on HF
ACT on Heart Failure (HF) aims to cut hospitalisations due to heart failure in half and improve survival rate by 20% by 2024.33 As part of this, we are working with multiple stakeholders to drive policy change, empower patients and caregivers, disrupt the diagnosis of heart failure and redesign diagnosis pathways. By the end of 2022, 45 countries had implemented programmes that have reached more than 20 million patients and 188,000 HCPs.33 For example, through Project OPERA in collaboration NHS Greater Glasgow and Clyde, the West of Scotland Innovation Hub, the University of Glasgow and other partners, we have enhanced heart failure care in Glasgow, Scotland, reducing echocardiogram waiting times down from 12 months to six weeks.34-36 Early diagnosis means patients can start appropriate heart failure treatment and reduce the risk of hospitalisation and death.
Spotlight On Heart Failure
This campaign aims to shine a light on this challenging condition, raising awareness about the symptoms of heart failure and inspiring people to take positive action. Based on the latest research, it's informed by those who know heart failure best - people living with the condition.
The Spotlight on Heart Failure campaign has been developed in partnership with the World Heart Federation and Global Heart Hub.
Procella Therapeutics
Our scientists, in collaboration with Swedish biotech company Procella Therapeutics and the Karolinska Institute, are advancing the prospect of cell therapy in heart failure. Together, we have successfully differentiated stem cells into human ventricular progenitor (HVP) cells that can form new cardiac tissue. In preclinical research, we have seen how these HVP cells, when injected into a damaged heart, engraft, proliferate and develop into beating ventricular cardiomyocytes like those in a healthy heart, leading to improved cardiac function.37 This research could help us achieve our ambition to form new cardiac tissue via remuscularisation of the heart, and ultimately, aim to cure patients with heart failure.
Our people
Built on an impressive legacy in CVRM research, we are uniquely positioned to build a healthier and longer future for people with these diseases. Our team of over 1,000 people spans more than 23 functions including early and late R&D, medical and commercial.
Our employees are accomplished and experienced scientists, researchers, clinicians, and healthcare and commercial professionals dedicated to advancing novel science and driving practice change to benefit patients with CVRM diseases.
References
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