Heart failure news and stories
Precision medicine in heart failure
R&DMaking heart failure a global health priority to transform patient care
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Heart failure
Home / Our therapy areas / Cardiovascular, Renal and Metabolism (CVRM) / Heart failure
Heart failure is a 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.
Unravelling the complexity of heart failure and CVRM diseases
The connections between cardiovascular, renal, and metabolism (CVRM) diseases continue to be elucidated as studies have found:
- Significant percentages of heart failure (HF) patients also have diabetes;5
- Cardiovascular disease (CVD) can lead to HF, and accounts for almost one-third of deaths in patients with late-stage chronic kidney disease (CKD) (stages 3-5)6; and
- Many patients with HF or CKD experience hyperkalaemia.7,8
The kidneys and heart are so closely connected that identifying risk factors, like CKD, and intervening early can help slow disease progression and reduce CV events.9
We are advancing research into interconnected disease drivers where we can intervene early, such as systemic chronic inflammation, a key driver of disease and influenced by several factors, including obesity and dyslipidaemia.10 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 heart failure with preserved ejection fraction (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 heart failure with reduced ejection fraction (HFrEF) and HFpEF, and those with CKD.
With the advances in genomics and other omics technologies, we are uncovering genetic disease drivers in specific subpopulations to enable us to better tailor treatment regimens. By considering different common molecular mechanisms of CVRM diseases, 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 incredibly complex diseases, so we can work towards developing the right treatment for the right patients.
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.11-15 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.12,13 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.16,17
Transthyretin-mediated amyloidosis (ATTR) is one type of amyloidosis and occurs when the liver produces transthyretin (TTR) proteins that are unstable, leading to a breakdown into its individual monomer components that are prone to misfolding and aggregating, forming amyloid deposits.18,19 ATTR can be either hereditary (ATTRv) or non-hereditary (wild-type) (ATTRwt).12
Two types of ATTR are ATTR-CM, which can cause heart failure (cardiomyopathy) and ATTRv-PN, which affects function of the peripheral nerves (polyneuropathy).13,14 ATTR-cardiomyopathy (CM) is a systemic, progressive and fatal condition that can lead to heart failure within several years of onset.13 As the TTR protein fibrils accumulate, more tissue damage occurs, the heart gets stiffer and the disease worsens, resulting in poor quality of life and eventually death.12,13,20,21
ATTR-CM can lead to a heart failure (HF) subtype known as HF with preserved ejection fraction (HFpEF), which occurs when the heart is unable to fill with blood sufficiently, due to increased stiffness of the muscle in the left ventricle and its inability to relax.22-24 ATTRv-PN leads to peripheral nerve damage and motor disability.25 Some patients may present as mixed phenotype and exhibit both CM and PN symptoms, which may complicate diagnosis and disease management.14,26
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).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 with 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 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.
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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Veeva ID: Z4-66921
Date of preparation: October 2024