Cardiovascular Health - Q1 2023

“There are more than 30,000 out-of-hospital cardiac arrests every year in the UK, but less than 1 in 10 people survive. ”

Dr

Corinne – Living with Heart Failure

If you have these symptoms:

Breathlessness

E xhaustion

Ankle swelling

Time to speak to your GP surgery

“Surveys suggest that more than 50% of AF patients are minimally aware of the risks or unaware they have AF.”

“We just don’t talk about Heart Failure enough. Together we can BEAT HF.”

Charmaine Griffiths, Chief Executive, British Heart Foundation

Daniel José Piñeiro, President, World Heart Federation

Patients should be equipped with the right resources and connections to advocate for their heart health and feel empowered to make decisions that work for them.

It’s every patient’s right to be involved in their own healthcare decisions. That means being as clued up as possible about their condition, notes Pat Khan, a Patient Representative with British Heart Valve Society (BHVS).

Thorough education on the disease

“Healthcare is increasingly virtual and, after Covid, getting access to GPs isn’t always easy,” she says. “To close the widening gap between patients and healthcare teams, it’s vital that patients do their homework properly. They must understand the best pathway and timeline through their disease, including the pros and cons of various treatments. Patients should know all the options to ensure that clinicians listen to their concerns and preferences.”

This can be challenging, particularly when it comes to heart valve disease — so being directed to the right resources and support is crucial. “The internet is an unreliable resource,” says Pat. “It’s why I refer patients to the BHVS website where they will find information about their condition, what to expect and their rights to treatment.”

Positive connections via patient-to-patient support groups

Thanks to social media, some patients can connect during and after treatment through patient-to-patient support groups to discuss their own experiences and concerns.

Charities such as the Ticker Club — an association of ex-heart surgery and cardiac procedure patients from Wythenshawe Hospital, Manchester — operate nearly daily visits to cardiac wards to offer patients emotional support.

“Patients can be in an extremely vulnerable mental state,” says Pat, who is part of the Ticker Club team. “They want to talk to someone who knows what they are going through, so they need well-informed volunteers to support patients with valve disease or other cardiac conditions.”

Pat believes that apps should be available to make it easy for patients to connect; while helplines should directly connect patients to specialist clinics and dedicated nurses; and forums allow patients and volunteers to meet and discuss how to optimise patient pathways.

“There are pockets of expertise, interest and passion in this field,” she says. “But a more joined-up approach is needed.”

Free online CPR training will only take you 15 minutes

There are more than 30,000 out-of-hospital cardiac arrests every year in the UK, but less than 1 in 10 people survive.

The British Heart Foundation (BHF) is asking the nation to take just 15 minutes to learn CPR. Someone’s chance of survival can double if they receive immediate CPR and defibrillation, and RevivR can make it easy, free and quick for everyone to learn these lifesaving skills.

Mobile CPR training RevivR has been designed for everyone to use, whether this is the first time you’ll be learning CPR or want to brush up on your existing skills. With no specialist equipment required, just a mobile phone and a cushion, it can give anyone the confidence to step in and save a life in the ultimate medical emergency.

you need is 15 minutes, a phone and a cushion to learn CPR through our online tool — it could teach you the skills to save a life.”

Connect to save a life

Alongside RevivR, the BHF is also working to improve survival rates as one of the leading charities and health organisations behind The Circuit — the national defibrillator network. Launched last year, The Circuit connects community-based defibrillators to NHS ambulance services across the UK so that in those crucial moments after a cardiac arrest, they can be accessed quickly to help save lives.

All you need is 15 minutes, a phone and a cushion to learn CPR through our online tool — it could teach you the skills to save a life.

In just 15 minutes, users can learn how to recognise a cardiac arrest, perfect their CPR technique by receiving live feedback and gain confidence in how to use a defibrillator. Learn CPR here: revivr.bhf.org.uk/.

Dr Charmaine Griffiths, Chief Executive of the British Heart Foundation, explains: “With over 30,000 out-of-hospital cardiac arrests every year in the UK and a survival rate of less than 1 in 10, there is an urgent need for people to learn CPR in an accessible and engaging way. All

It’s estimated that public-access defibrillators (PADs) are used in less than 1 in 10 out-of-hospital cardiac arrests across the UK — often because 999 call handlers aren’t always aware that a defibrillator is available nearby because the ambulance service hasn’t been told about it.

To help save more lives, the BHF is urging people who look after defibrillators in places such as offices, communities, shopping centres and leisure centres, as well as in public places, to register them on The Circuit.

Why valve patients with the right resources engage in better decision-making

Why we need to do more to highlight the dangers of heart valve disease

The public needs to have a greater awareness of heart valve disease, a predominantly age-related condition which can be potentially fatal if left undiagnosed and untreated.

It is estimated that 1.5 million people in the UK have significant heart valve disease, a potentially fatal condition which is increasingly common above the age of 65.

Irreversible damage to heart chambers

John Chambers Emeritus Professor of Clinical Cardiology at Guy’s and St Thomas’ NHS Foundation Trust

WRITTEN BY Tony Greenway

Among the public, heart valve disease may not be as well-known as other cardiac conditions, such as angina or heart failure. That needs to change, insists John Chambers, Emeritus Professor of Clinical Cardiology at Guy’s and St Thomas’ NHS Foundation Trust, particularly because heart valve disease is a predominantly age-related disease — and, as we are all living longer, more of us will be affected by it.

“People need to understand that valve disease can cause irreversible damage to the pumping chambers of the heart and is an important underlying cause of heart failure,” he says. “Indeed, undetected aortic valve diseases affect 10% of heart failure patients. As such, it requires much wider attention than it currently receives.”

Causes of valve disease and available treatments

Professor Chambers explains: “The heart has four valves — aortic, mitral, pulmonary and tricuspid — which open to let blood flow in and then close to prevent reflux when the heart contracts. As we age, the aortic valve can progressively degenerate and calcify, restricting healthy blood flow; while a weakness of the mitral valve can prevent it from closing completely, causing blood to flow in the wrong direction. Apart from age, heart valve disease can be caused by congenital abnormalities and infections such as rheumatic fever and infective endocarditis — so it affects younger people too.”

The good news, according to Professor Chambers, is that “treatment is available and includes valve repair or replacement procedures. Where surgery is not suitable, a transcatheter aortic valve implantation (TAVI) procedure may be used to insert an artificial replacement valve into the heart.”

Why diagnosis times and care must be optimised

The challenge is catching heart valve disease in time.

“Patients often display no symptoms in the early stages of the condition, so it can be a silent killer.

Valve disease is only detected in about one-half of patients,” says Professor Chambers.

“It’s so important for clinicians to check their patients for signs of a heart murmur. Anyone with a murmur or other cardiac symptoms can then be

referred for a basic ultrasound scan (echocardiogram) to determine if more extensive echocardiography is needed.” Speed is key because, apart from increasing surgical risks, later diagnosis can limit recovery.

Another issue that needs addressing is that care for valve disease is often still performed by physicians without specialist competencies in the condition. “Each healthcare location should have a dedicated specialist who is able to read the latest valve disease guidelines and research,” says Professor Chambers. “Only 66% of cardiac centres have valve clinics. These clinics, or the requirement for specialist competencies, need to be universal.”

Importance of patient education and engagement

Finally, patient education and engagement should be improved. “Education regarding the disease should occur by a discussion with the patient over some time,” says Professor Chambers.

“The clinician can then advise the patient about the treatment options open to them, while the patient can educate the clinician about the type of treatment they want. Overall, results will be better if patients are involved in decision-making.”

This is why it’s important that patients understand as much about the condition as possible, stresses Professor Chambers. “They can be in a better position to assimilate information, ask questions, challenge decisions and, ultimately, drive up medical standards. I feel very strongly that the way forward must include educated and engaged patients.”

INTERVIEW WITH

Apart from age, heart valve disease can be caused by congenital abnormalities and infections such as rheumatic fever and infective endocarditis — so it affects younger people too.

Tracing the steps to better cardiovascular health

It is preventable and treatable, so it might surprise people that cardiovascular disease claims more lives every year than even cancer — more than 18 million.

WRITTEN BY Daniel José Piñeiro President, World Heart Federation

Cardiovascular disease (CVD) can strike anyone, manifest in different ways and have varying causes. High cholesterol, tobacco, physical inactivity and harmful use of alcohol are factors that can compromise cardiovascular health. Additionally, air pollution is a growing risk that complicates cardiovascular conditions.

Working towards better cardiovascular health

As for all diseases, habits and genetics play a role. For some, the hereditary (genetic) component is the most important. For example, Familial hypercholesterolemia (FH) is an inherited, metabolic disorder. Individuals with FH have high levels of low-density lipoprotein (LDL) cholesterol — sometimes called ‘bad’ cholesterol — due to a mutation in one of several genes that help regulate and eliminate it.

Guidance in a series of WHF Roadmaps can be a timesaver. They help map challenges, stakeholders and options across systems to support responses that might not always be considered or obvious. With case studies and examples, the series synthesises challenges and solutions and makes practical recommendations.

A closer look at cholesterol for cardiovascular health

High cholesterol is a factor in the deaths of more than 4 million people every year.

Elevated levels of unhealthy cholesterol (low-density lipoproteins or LDL-C) can lead to plaque build-up or atherosclerosis that causes arteries to narrow and increases the person’s risk of heart attack and stroke.

Obstacles to managing cholesterol often include a lack of health awareness and education, insufficient or delayed screening or poor access to health facilities and treatments.

As the Roadmap on Cholesterol shows, food labelling and regulation plus taxes on unhealthy commodities are some concrete steps to prevent unhealthy cholesterol levels. Timing matters, too; population-level screening can identify atrisk individuals. Equitable policies are a must: knowledge and evidence, effective drug treatment and supporting modified lifestyles can ensure people access care.

Hypertension: common yet manageable

Often causing no overt symptoms, raised blood pressure or hypertension can impair the functioning of the brain, heart and kidneys. An estimated 1.3 billion people live with hypertension with only one

in five having it under control.

With ageing and certain lifestyle habits, maintaining blood pressure at an ideal level can be challenging. According to The Roadmap on Hypertension, government health policies that emphasise initial screening for hypertension from 18 years of age — and repeated regularly — can identify problems as part of primary prevention or treatment.

Combination therapies — for example, via a single pill in some cases — can improve patients’ adherence to treatment and help simplify processes in primary care.

Arrhythmia awareness

Atrial Fibrillation (AF or AFib), is the most common arrhythmia, affecting more than 33 million people worldwide. In AF, the atria beat out of normal rhythm, causing blood to be pumped less efficiently.

Surveys suggest that more than 50% of AF patients are minimally aware of the risks or unaware they have AF. The WHF Roadmap on Atrial Fibrillation emphasises the issues and opportunities for addressing AF. Challenges encompass access to clinics, especially for those in rural areas.

One important impetus for the updated Roadmap has been the addition of treatments to the World Health Organization’s Model List of Essential Medicines vetted for their safety and effectiveness in meeting global health needs.

Tech for better cardiovascular health

There are digital health interventions (DHIs) including text messaging platforms, mobile (mHealth) apps, wearable devices and more. The Roadmap for Digital Health in Cardiology assesses the opportunities for DHIs to tackle cardiovascular disease.

Healthcare secured this way can expand equitable access to help reduce the incidence and mortality of cardiovascular disease. DHIs can take the strain off workforce capacity and support tasks that can be undertaken virtually.

To learn more, visit WHF Roadmaps. The World Heart Federation (WHF) represents the global cardiovascular community, uniting over 220 members such as heart foundations, scientific societies, patient organisations and civil society groups in more than 100 countries to share knowledge and advocate for heart health for everyone. Visit worldheart.org

With ageing and certain lifestyle habits, maintaining blood pressure at an ideal level can be challenging.

How a TAVI heart procedure made an 82-year-old patient active again

Wendy McCarthy, 82, talks about the importance of seeking help from healthcare professionals when symptoms progress and how the transcatheter aortic valve implantation (TAVI) procedure has given her a new lease of life.

After leading an active life into her early 80s, enjoying her garden and spending time with friends, former schoolteacher Wendy McCarthy found that she was increasingly feeling unwell.

She was becoming breathless, and as her symptoms persisted, she had tests with her GP and was given an inhaler at one stage. Then, one evening, she was particularly ill and called her daughter and an ambulance.

Wendy found herself in the A&E department at her local hospital in Peterborough. As she drifted in and out of sleep, she turned to her Christian faith and asked her family to read from the Bible, fearing her life was nearing its end.

Further heart investigations

At the hospital, Wendy was offered palliative care, though her brother felt there were other options and pushed for further investigation.

They found that she had aortic stenosis, and her heart valve needed replacing. She was moved to the cardiology ward; however, she suffered a further setback when she contracted pneumonia and had to recover before the heart procedure could resume. After spending four weeks in hospital recovering, she was transferred to a specialist cardiac hospital, Royal Papworth Hospital NHS Foundation Trust in Cambridge — just before Christmas 2021.

TAVI heart procedure

Wendy had a history of heart problems as she had a heart attack in 1998 after losing her husband to prostate cancer.

After that, she had regular checks on her health including cholesterol readings but led a full and active life. When she fell ill again, her family provided support.

Once she came under the care of the cardiology team at Royal Papworth Hospital NHS Foundation Trust, they decided that she was suitable for a TAVI procedure, which went ahead just before Christmas 2021.

Wendy wasn’t afraid of getting the procedure done. Expecting the procedure to take place at 14.00, she was pleasantly surprised that it was moved forward to the morning. “I was excited, I was desperate to have the procedure and get better,” she recalls.

is for the living.

Building strength back

Having been conscious throughout the procedure, Wendy was well enough to be discharged on December 27. Patients can usually go home after 48 hours, but Wendy stayed in hospital a few days longer as her procedure was over the festive period.

While her recovery from the TAVI procedure was quick and easy as expected, she needed a bit more time to get back to her fullest after being bed-ridden due to her pneumonia.

“My daughter got my house ready for my return home, but I needed lots of rest to recover,” she says. “Basic tasks like filling the kettle were a strain on my muscles, but later, I was able to begin rehabilitation in order to build strength back.”

With her family living close by, they were able to offer her continuous support, but now, Wendy is well on the road to recovery and was even able to drive to her final rehabilitation session.

New lease of life

Only a short time after her TAVI procedure, Wendy says she’s been given a “new lease of life.” She drives, visits her church again and has been able to regain much of the joy and energy she lost due to the illness.

With a love of gardening and meeting up with friends every week, a positive attitude has contributed to her recovery. “Life is for the living,” she says.

Heart care advice she would give to others is: “Be very careful about what you eat; avoid fats; and eat chicken, fish and vegetables; eat wisely and exercise.”

She insists that people should not worry about having the TAVI procedure. “It’s not scary, doctors know what they are doing,” she adds. “I would not be here if I had not had it done.”

For more information on aortic stenosis, the TAVI procedure, and life after TAVI, scan the QR code or visit newheartvalve.co.uk

INTERVIEW WITH Wendy McCarthy

Life

INTERVIEWED BY Emma-Jean Edwards

Saving lives by changing the trajectory of heart failure

Cardiovascular diseases are the leading cause of death in the UK and globally, accounting for about a third of lives lost each year. Everyone knows someone who has — or had — a ’heart problem.’ They may or may not call it heart failure. We are at a crucial point in time to address this problem.

Over 1 million people in the UK have heart failure, with 200,000 new diagnoses every year. Estimates suggest there are a further 385,000 people with heart failure who are currently undetected and undiagnosed and, consequently, missing out on life-preserving treatments. These numbers are on the rise due to several factors including the exponential growth in population anticipated in the next 25 years.

The need to manage heart failure

Heart failure is not only a primary endpoint for almost all cardiovascular diseases but also a significant cause of mortality across the wider cardiorenal-metabolic spectrum (which includes conditions such as diabetes and kidney disease). And from epidemiology to pathophysiology, there are overlaps with many other organ systems and clinical specialities.

Currently, in the UK, 80% of heart failure is diagnosed in hospitals but 40% of people had symptoms that should have triggered an earlier assessment in primary care. Heart failure takes up 2% of the entire NHS budget. The human and economic costs are huge.

The F words: common symptoms of heart failure

Identifying people at risk of developing heart failure and intervening early is key to the long-term management of cardiovascular diseases. Identified early, we can make a huge difference in the lives of those with heart failure. We have the tools and expertise to manage heart failure well. We need you to look out for the common symptoms of heart failure — the ‘F words’: ‘fighting for breath,’ ‘fatigue’ and ‘fluid retention.’ If you recognise any of these in yourself or your loved ones, seek medical help early. A simple blood test (NTproBNP) can be used to rule out heart failure or indicate the need for further tests.

Despite growing success due to scientific breakthroughs and increasing awareness and understanding, we must change the trajectory of heart failure, which will lead to sustainable wins across other diseases.

Collaboration to reduce heart failure deaths

We cannot rely on government plans, which are vulnerable to seemingly constant change and short-termism. By working together with allied organisations and looking through the lens of our population’s health, we can accelerate action towards reducing deaths due to heart failure in the next 25 years.

As a collective, we will leverage our reach, infrastructure and human capacity to build a more equitable, inclusive, prosperous and sustainable future for all those in danger of dying from heart failure, regardless of circumstances. Together, we can turn the tide on this life-limiting condition and benefit our communities. To achieve this, we intend to:

1. Commit to taking collective action for change

2. Bring together our specialist knowledge and professional expertise

3. Support implementation through localised communities

4. Embed better prevention programmes and early detection to improve population health

This month, March 2023, we commit to uniting as leaders towards a common goal — to reduce heart failure deaths by 25% in 25 years. Beginning with agreeing on the priorities at a summit meeting, together, we can save lives.

WRITTEN BY Lynn Mackay-Thomas Chief Executive Officer, British Society for Heart Failure

A simple blood test (NTproBNP) can be used to rule out heart failure or indicate the need for further tests.

Why AI is proving to be a force for good in cardiovascular health

Two experts in the field of cardiology say that AI will transform life for patients with suspected heart problems because it can improve diagnosis with timely and accurate referrals.

Heart disease is a leading cause of death in the UK, causing one in four deaths and affecting an estimated 7 million individuals yearly.

Can you explain how the typical journey of a cardiac patient begins?

JB: Patients with heart disease can present with different symptoms, including chest pain, palpitations, dizziness and shortness of breath. If symptoms are mild, the beginning of their journey would be to see their GP, who, typically is the gatekeeper to specialised care. If the GP decides their condition needs further investigation, they will be referred to a cardiologist. When symptoms are severe, patients would go to the hospital’s A&E department or be taken to emergency care by ambulance.

cardiac cases, even if entirely innocent. In other cases, they can overlook conditions that could have serious and potentially fatal consequences — if not dealt with in time.

To address this challenge and need, we have developed a diagnostic tool called PMcardio which can digitise and analyse any ECG within seconds — and diagnose up to 38 cardiovascular diseases — be it in a primary or emergency care setting. It uses our certified AI technology to harness knowledge from millions of previous patients providing outputs with unmatched precision and speed.

What advantages does this device offer to healthcare professionals?

RH: By combining the precision of AI ECG interpretation and the contextual analysis of the patient’s symptoms and medical history, it can recommend the referral decision and treatment plan — as if the healthcare professional had a cardiologist sitting right next to them.

PMcardio is MHRA registered, MDR CE-certified and has been launched commercially in the UK, accessible in the form of a simple smartphone application. It is available for healthcare professionals in the NHS and is being used in several practices throughout the country.

How can AI technology influence the cardiac patient journey from the perspective of cardiologists?

Cardiologists know the importance of appropriate timing and efficiency in providing the best care for patients. We are often inundated with referrals of concerned patients, mainly seeking reassurance.

What diagnostic tools aid in the diagnosis and management of cardiac patients at the first point of contact?

RH: The GP reviews the patient’s medical history and performs clinical examinations. They record an ECG (an electrocardiogram, a test which detects the heart’s rhythm and electrical activity), which is one of the most-performed and accessible diagnostic tests available at the first point of contact, also used by paramedics for patients in A&E.

What are the obstacles at the first point of contact, and how can technology solve this?

RH: A major obstacle is that ECGs can be difficult to interpret. GPs who do not specialise in cardiology tend to be cautious and refer the patient further. However, the problem with that is that emergency and cardiac departments are often overwhelmed with suspected

If a diagnostic solution is available that is quick and tailored to each individual patient and can streamline the referral pathway, it can dramatically improve patients’ outcomes and wellbeing. This means that cardiologists and emergency services can triage patients optimally and address the appropriate treatment to those in most urgent need.

Which research and development initiatives will have the most significant impact on the care of cardiac patients?

RH: We are developing technology that can predict potential risks of cardiac patients before symptoms become visible, so they can change their lifestyles and/or be given preventative treatment.

Our AI algorithms will allow for an analysis of seemingly normal ECGs and detect any occurrences of arrhythmia or precursors to heart attacks. This will turn PMcardio from a detection tool to a prevention tool, making it crucial for physicians to have access to this technology.

WITH Prof. Dr Jozef Bartunek, PhD Associate Director at the Cardiovascular Center in Aalst and visiting professor at the University of Leuven

INTERVIEW WITH Dr Robert Herman Digital and Innovation Committee Member, European Society of Cardiology Chief Medical Officer, Powerful Medical

Cardiologists and emergency services can triage patients optimally and address the appropriate treatment to those in most urgent need.

WRITTEN BY Tony Greenway

Why we won’t accept that high cholesterol is just a part of ageing

To reduce the risk of heart attacks, the key is to lower the levels of so-called ‘bad’ cholesterol as much as possible for as long as possible.

Despite what you may have heard or read, high cholesterol — a lipid (or fat) produced in the liver — isn’t just a normal part of ageing. Getting the cholesterol as low as possible for as long as possible is probably the best way to treat as well as avoid a heart attack.

The big problem is that, due to genetics, lifestyle and/or diet, many of us have far too much low-density lipoprotein cholesterol (LDL-C) — so-called ‘bad cholesterol’ — storing up a time bomb of trouble in our blood vessels. Without treatment, this can lead to atherosclerotic cardiovascular disease (ASCVD), a condition that can have serious and sometimes fatal repercussions.

“Problems occur when cholesterol starts building up in the walls of our arteries,” explains Dr Andrew Bellinger, Chief Scientific Officer and Chief Medical Officer of genetics medicines company, Verve Therapeutics. “When we’re younger, this is just a sort of fatty smear; but, over time, it can cause inflammation and plaque buildup. If larger, fattier, unstable plaque deposits rupture, they can block an artery. This can lead to a heart attack or stroke, which is the leading cause of death in the world right now.”

People with low LDL-C are more resistant to heart attack

The statistics are alarming. In England, heart disease accounts for around a quarter of deaths, with 140,000 people dying from the condition each year, according to the NHS. To reverse this trend, it’s crucial to get LDL-C levels as low as possible, for as long as possible, insists Dr Sekar Kathiresan, Cofounder and Chief Executive Officer of Verve Therapeutics.

“People with high levels of LDL-C are more likely to suffer a heart attack,” he says. “Extensive research has shown that we are all probably meant to live with an LDL-C around 1 mmol/L. Those who have naturally occurring DNA variation that keeps their LDL-C low are more resistant to heart attack and ASCVD.”

Inefficiencies of the chronic care model for ASCVD

Traditionally, lowering cholesterol has meant taking daily treatment, such as statin medication, often for decades. However, Dr Kathiresan believes this is part of a broken — and expensive — model of chronic care. “CVD-related healthcare costs in England are estimated at £7.4 billion per year,” he says, “with annual costs to the wider economy estimated at £15.8 billion, according to the UK Health Security Agency.”

The fact is that only half of the people who should be taking cholesterol-lowering medication actually do. There are a few reasons for this, but the main one is that the chronic care model of daily pills or intermittent injections over decades places a heavy burden on patients, providers and the healthcare system.

Treating the disease with a breakthrough once-and-done approach

In what promises to be an exciting breakthrough development for the field of cardiology and cardiovascular disease, Verve Therapeutics is pioneering a new approach to ASCVD with a once-and-done gene-editing medicine designed to durably lower LDL-C after a single intravenous infusion. In animal models, this investigational medicine has been shown to lower LDL-C by up to 70% with durability for more than two years, raising the possibility of a once-and-done treatment for LDL-C and ASCVD.

“There’s a belief that high cholesterol and its associated risks are just a normal part of ageing that we have to accept,” says Dr Bellinger. “We’re saying that it really doesn’t have to be that way. And we won’t accept it. High levels of LDL-C are a leading contributor to heart attack and current treatment options are too burdensome to address a majority of patient needs. A once-and-done treatment has the potential to protect the world from cardiovascular disease.”

SPREAD INTERVIEW WITH Dr Sekar Kathiresan Cofounder and Chief Executive Officer, Verve Therapeutics

SPREAD WRITTEN BY Tony Greenway

SPREAD INTERVIEW WITH Dr Andrew Bellinger Chief Scientific Officer and Chief Medical Officer, Verve Therapeutics

Spread paid for by Verve Therapeutics

How breakthrough gene-editing medicines could lower cholesterol — permanently

Finding a way to prevent and treat heart attacks is a personal quest for Dr Sekar Kathiresan, Cofounder and Chief Executive Officer of genetics medicines company, Verve Therapeutics.

“Like so many families, ours has lost loved ones to cardiovascular disease,” he says. “My grandmother, uncle and brother all died of premature heart attacks. Both my uncle and brother were only 42 years old when they passed. My family’s experience led me to these questions: Why do some people have heart attacks at a young age — and might some be naturally protected?”

Dr Kathiresan found the answers when he and other human genetics researchers discovered people who naturally lacked any of several cholesterol-raising genes including PCSK9 and ANGPTL3. This meant they had a disease-causing gene permanently switched off, leading to very low levels of low-density lipoprotein cholesterol (LDL-C, so-called ‘bad cholesterol’) in their blood and, as such, were naturally protected from the risk of heart attacks. “Whereas, people with high levels of LDL-C are more likely to suffer a heart attack,” explains Dr Kathiresan.

The ability to permanently switch off a disease-causing gene

This discovery led to Verve’s mission to develop a pioneering medicine: one that mimics natural protection by turning off the PCSK9 gene in high-risk people, thereby with the potential to powerfully lower their LDL-C levels. “To do this, we chose

a second generation gene-editing technology called base editing,” explains Dr Andrew Bellinger, Chief Scientific Officer and Chief Medical Officer at Verve Therapeutics.

“First generation gene-editing technology cuts the DNA in the gene in a specific location. However, base editing is an even more targeted approach which provides us with the potential to permanently change a disease-causing gene. Rather than cutting it, it’s more like correcting a spelling error with a pencil eraser.”

This new approach — called VERVE-101, which is now at the clinical trial stage — is delivered as a one-time intravenous medication. It could be good news for people struggling to control high cholesterol with daily pills or intermittent injections. “Despite the medicines we have available to treat cholesterol, only about half the patients who have suffered a heart attack are currently taking an LDL-C lowering medicine,” says Dr Bellinger. “The chronic care model requires daily pills or intermittent injections over decades and places a tremendous burden on patients, providers, and the healthcare system, leading to a large unmet need. We hope to offer patients a new option – a one-time treatment, permanent lowering of LDL-C.”

Innovation passport to speed drug development

The company hopes that it will be able to use VERVE-101 to dramatically alter treatment for heterozygous familial hypercholesterolemia (HeFH), an inherited genetic disorder that causes

high cholesterol, and ultimately, ASCVD. Nevertheless, Dr Bellinger admits there’s still a long road ahead before this medication becomes available to patients on the NHS.

“We’re extremely grateful to the participants in our study for trusting us and furthering our understanding of HeFH,” he says. “At present, we’re running a clinical trial in New Zealand and the UK, with regulatory clearance from the MRHA (Medicines and Healthcare products Regulatory Agency), the UK regulatory authority.

“We’ve also received an innovation passport from MRHA and NICE (National Institute for Health and Care Excellence) that is designed to accelerate drug development and access in the UK to novel therapies. We’re hopeful that it will help speed up the process so that we can make it available to everyone who needs it.”

A future with less risk of heart attacks

Ultimately, Dr Kathiresan and Dr Bellinger believe that the therapy will be a medical game-changer. “It won’t just revolutionise the way we lower cholesterol,” says Dr Bellinger.

“It could revolutionise the whole field of cardiology and cardiovascular disease. This is how we will treat heart disease in the future. We won’t wait for someone to have a heart attack, give them a stent and put them on five different medicines. Instead, we will be lowering their risk of heart attacks earlier by lowering their LDL-C with one-time therapies. That’s a really exciting thought.”

Gene-editing medicines that permanently and significantly lower cholesterol and the risk of heart attacks could revolutionise the field of cardiovascular disease.

Fainting could be caused by something more serious — don’t ignore it

Fainting — or syncope — is a temporary loss of consciousness caused by a decrease in blood flow to the brain, and 50% of the population will faint at least once in their lifetime.

Thirty years ago, I started the charity STARS (Syncope Trust And Reflex Anoxic Seizures), following the diagnosis of my daughter with RAS (Reflex Anoxic Seizures) — the most severe form of fainting.

Fainting is traumatic for the patient and never simple

Most people are unaware that fainting could be a warning sign for a potentially serious and life-threatening heart condition. In many cases, fainting is the only sign of an abnormal heart rhythm which is a leading cause of SCA (sudden cardiac arrest) — a devastating condition that kills 100,000 people in the UK alone each year. A history of fainting is often the only symptom prior to SCA.

Facts about fainting

• Approximately 30% of adults and 39% of children misdiagnosed with epilepsy have an underlying (and often fatal) heart rhythm defect, known as an arrhythmia.

• One in three visits to A&E are due to syncope but many are mistaken for epilepsy.

• Among the elderly, falls may be due to syncope. They often end up in residential care and lose their independence, but if syncope was diagnosed and treated with a pacemaker, they could remain independent and lead active lives.

How complex heart surgery can give you your life back

Paul Le Breton kept a close eye on his heart condition. Having undergone heart surgery in 2008 to replace his faulty aortic valve, Paul knew that within 15 years, his bioprosthetic valve would likely begin to wear out.

Iknew my valve was possibly getting near the end of its life,” says 58-year-old Paul, owner of an auto repair garage in Guernsey.

“So, I had some tests done locally.”

Necessary heart surgery

Consultant Cardiac Surgeon

WRITTEN BY Angelica Hackett O’Toole

Paul underwent testing in 2020. After being monitored for two years, his cardiologist reviewed new test results that showed a startling discovery. Not only was Paul’s replacement valve working at just 20% capacity, but he also developed an aortic aneurysm — which could be life-threatening if it were to rupture or split.

“My doctor said, ‘You need to get this repaired within two weeks,’” recalls Paul. “It was a complete shock to me.

The difficulty of diagnosis

The challenge in correctly diagnosing syncope or RAS is that by the time the person sees a doctor or reaches a hospital, they have recovered consciousness. The symptoms experienced before losing consciousness can last only seconds or occasionally one to two minutes, and the period of unconsciousness itself can be even less, at 20–30 seconds. Full recovery, in most cases, is within one hour. Witness information is therefore important.

Campaigns to help people get diagnosed

To raise awareness of fainting and its possible link to fatal heart rhythm conditions, STARS launched ‘Take Fainting to Heart,’ a campaign encouraging people to take fainting more seriously and contact their GP after unexplained unconsciousness. As per guidelines, they can then have a 12-lead ECG to monitor the rhythm of the heart and ensure a heart rhythm specialist reviews the results.

Moreover, The Blackouts Checklist was produced to help individuals and their doctors reach the correct diagnosis for any unexplained consciousness.

For three decades, STARS has worked to raise awareness and educate about the importance of fainting and its links to possible heart rhythm conditions and to provide much-needed support to patients and their caregivers.

brothers suddenly suffered cardiac arrest and passed away. While devastated by the news, it reinforced the severity of Paul’s situation, and he went ahead with the surgery just days after his brother’s death.

He said there was one surgeon he would recommend to do it.”

Seeking an expert surgeon Paul immediately scheduled an appointment with Ranjit Deshpande, MBBS, FRCS, a cardiac surgeon at Cleveland Clinic London. The hospital opened in March 2022, and Paul and his wife, Emma, made the 45-minute flight to London to meet with Mr Deshpande.

“Paul’s artery was enlarged to almost six centimetres — a stage where it can rupture or lead to fatal bleeding,” notes Mr Deshpande. “He would need a major operation, and we couldn’t put it off for too long.”

Paul experienced a sudden and unexpected tragedy when one of his

Complex surgery with a great result

Mr Deshpande led a specialised team through a simulation the night before the surgery. The next day, they completed the procedure, during which he repaired the aneurysm and replaced the faulty aortic valve, which had begun leaking blood into Paul’s heart.

Mr Deshpande emphasises one of the most important parts of the process is post-operative care. Having an intensive care team, including a consultant anaesthetist available around the clock, ensures patients, like Paul, always receive the best care. Emma adds: “The staff were brilliant and so informative.”

Paul points to his care team as the key to his thriving recovery. “I’m back playing golf and working out in the gym,” he says. “I feel better than ever.”

WRITTEN BY Trudie Lobban

MBE FRCP Founder, STARS (Syncope Trust And Reflex Anoxic Seizures)

Having an intensive care team, including a consultant anaesthetist available around the clock, ensures patients, like Paul, always receive the best care.

INTERVIEW WITH Mr Ranjit Deshpande, MBBS, FRCS

Monitoring blood pressure at home helps prevent the risk of heart attack and strokes

White coat and masked hypertension

Dr Yassir Javaid, a GP with a specialist interest in cardiology, says: “Multiple readings at home, averaged out, is a much more accurate reflection of day-to-day blood pressure than having a reading done in a clinic.”

GPs no longer tend to base diagnosis and treatment of hypertension on clinic readings. He also pointed to the phenomenon of ‘white coat hypertension’ where patients can have elevated blood pressure in the clinic but normal blood pressure at home. However, he emphasises that white coat hypertension should not be dismissed as those patients may develop hypertension in the future. There is also ‘masked’ hypertension where patients display normal levels of blood pressure in clinical settings but actually have elevated blood pressures elsewhere. With home blood pressure monitoring, patients and GPs will be able to see these readings.

Home blood pressure monitoring can help a doctor make the diagnosis and monitor the treatment of hypertension which leads to reduced risk of serious cardiovascular events such as heart attack and stroke.

In the past, high blood pressure — or hypertension — has often been diagnosed via a ‘snapshot’ one-off reading in the GP surgery or clinic. But health experts acknowledge that this approach often delivered inaccurate outcomes.

Average reading

Patients are now asked to measure their blood pressure in the comfort of their homes over seven days to ascertain an average reading.

The recommended approach is for people to sit down, relax and take two or three readings, one minute apart in the morning and the evening. This can deliver a more accurate reading and leads to better diagnosis.

Professor Neil Poulter says that the majority of people over 60 can be affected by high blood pressure. “It is a common problem … with 10.8 million deaths each year due to raised blood pressure,” he says.

In the UK, 30% of adult men and 23% of adult women have hypertension. Measuring blood pressure at home with a clinically validated blood pressure monitor

helps to get an early diagnosis and can advance achieving target values in combination with telemonitoring.

Silent killer

Clinicians call it the ‘silent killer’ because it rarely has symptoms, and many people do not even know they have hypertension, which can lead to heart attack, stroke, vascular dementia and kidney failure.

Professor Poulter says home measuring is important to help clinicians diagnose the condition and prevent such cardiovascular events from occurring.

“That gives a much better view of what blood pressure is throughout the week rather than one snapshot reading in a GP surgery; this can better help predict cardiovascular events,” says Professor Poulter, who established the global blood pressure screening campaign May Measurement Month in 2017.

“We can then treat people with drugs and dietary measures to reduce their risk of heart attack and stroke.” He emphasises the importance of the correct usage of a machine that is clinically validated.

Benefits of home monitoring

Emphasising the value of home readings, Dr Javaid says: “This is about primary prevention of blood pressure because prolonged blood pressure can cause a variety of problems.”

Patients can share written blood pressure readings with their GP or send them digitally via devices such as the OMRON Connect app and device. Sharing data contributes to improved therapeutic compliance and achieving target values earlier, which reduces cardiovascular risks significantly.

Freelance journalist Liz Hoggard, 60, who has a family history of heart disease and high blood pressure finds the OMRON device helpful and easy to use. She regularly uses it and says she benefits from real-time assessment in a familiar environment, rather than going to a GP.

According to Hoggard: “The advantage is that the app displays the rolling average. Very early aggressive intervention can pretty much get rid of the excess risk, but the foundation is a healthy lifestyle before we even think about starting medication.”

Image provided by OMRON

Paid for by OMRON

Multiple readings at home, averaged out, is a much more accurate reflection of day-to-day blood pressure than having a reading done in a clinic.

INTERVIEW WITH Neil Poulter Cardiologist

INTERVIEW WITH Liz Hoggard Journalist and Author

WRITTEN BY Mark Nicholls

It’s important for cardiac patients to attend rehab programmes, says Dr Kathryn Carver, President of the British Association for Cardiovascular Prevention & Rehabilitation.

What are cardiovascular prevention and rehabilitation programmes?

These are free NHS programmes, delivered by healthcare professionals to BACPR standards, usually running over two to three months. They aim to empower people who have experienced a cardiac event with the confidence to manage their condition through better knowledge and exercise. Attendees can ask questions and address health concerns, particularly if they haven’t been able to see their GP.

How are the programmes delivered?

There are group sessions available outside hospital settings in local community locations, such as gyms and church halls. However, some patients may be happier to follow a programme at home via an NHS-approved app, or virtually via the web, and receive a regular follow-up phone call from a healthcare professional. It’s all about patient choice.

Who is eligible to attend?

Anyone who has had a heart event such as a heart attack, heart failure, cardiac surgery or angina. Patients can be referred to a programme by their GP, or they can self-refer. However, most attendees are referred after a hospital stay by their consultant or healthcare team.

What do the programmes involve?

Programmes include an educational component where patients are given information about how best to change behaviours to adopt healthier lifestyles, they also include advice on risk factors and medicines along with supervised or home exercise sessions. Patients are encouraged to keep healthy after the programme ends by accessing self-funded support services.

Which healthcare professionals are involved in the programme?

They can include cardiac nurses, physiotherapists, exercise professionals and dieticians. Psychological support is key, too, because cardiac events are often traumatic and isolating.

What’s your advice to patients who are nervous about attending?

Don’t be! We would urge every cardiac patient to come along and try it. These programmes are non-judgmental and so important. Patients can have a better quality of life and valuable peerto-peer support — and, if their healthy lifestyles continue, decrease risk of further cardiac events and reduce the chance of hospital readmission.

Lower is better for a healthy heart: keeping lipids under control

Heart attacks, strokes and angina are caused when fats (lipids) accumulate in the walls of our arteries. Keeping levels of harmful lipids low can prevent these deadly conditions.

Lipids, such as cholesterol are essential to life. However, almost half of UK adults have raised cholesterol which can lead to heart disease. Cholesterol is carried in a variety of lipoproteins. Low-Density Lipoproteins (sometimes called LDL-cholesterol or ‘bad cholesterol’) enter and remain in the walls of blood vessels. This causes heart attacks and strokes.

The process starts very early in life, with early stages seen in teens and twenty-somethings. To protect our health as we get older, it is essential to reduce LDL-cholesterol.

Keeping lipids low throughout life

Maintaining a healthy diet and making simple lifestyle changes can keep LDL-cholesterol levels low. Swapping saturated fats for unsaturated fats can reduce the levels of LDL-cholesterol.

The HEART UK website has information and healthy recipes for you to try. Additionally, cutting down on alcohol; avoiding smoking; and regular exercise are great ways to protect the heart.

Safe and effective drugs

We all produce cholesterol in our liver, and this can contribute to the risk of heart disease. This is especially relevant in people with familial hypercholesterolaemia, who have a genetic tendency to accumulate LDL-cholesterol. When someone

WRITTEN BY Dr Peter Penson Reader in Cardiovascular Pharmacology, Liverpool John Moores University; Medical Scientific & Research committee, HEART UK

For more information, visit heartuk.org.uk

has an increased risk of heart disease, medicines can be used together with lifestyle changes to give additional benefits.

The most common treatment for raised LDL-cholesterol is a family of drugs called statins. These drugs block the production of cholesterol in the liver.

Statins often work very well. They can reduce your LDL-cholesterol by around 30%, sometimes even 50% with high doses. This reduces the risk of heart attacks and strokes. When you start taking a statin, the prescriber will take blood tests to ensure that the drug is reducing LDL-cholesterol as expected.

All medicines cause side effects, and statins are no different. If you do experience side effects with statins, it is important to talk to your prescriber to resolve the issues together — simply stopping the medicine may put you at greater risk of heart disease.

Other medicines

Sometimes, even statins are not enough to reduce the LDL-cholesterol, and there are some patients for whom statins are not suitable. In this situation, a range of additional drugs is available depending on the patient’s circumstances. However it is achieved, the important thing is for everyone to keep LDL-cholesterol as low as possible for as long as possible to protect us from heart disease.

We all produce cholesterol in our liver, and this can contribute to the risk of heart disease.

How rehab programmes offer cardiac patients the way to a better quality of life

INTERVIEW WITH Dr Kathryn Carver President, British Association for Cardiovascular Prevention & Rehabilitation

WRITTEN BY Tony Greenway

The importance of lowering high cholesterol earlier

Identifying disease risk

If people take action early on, even modest decreases in cholesterol can have benefits, explains Professor Philip Calder, Head of Human Development & Health, University of Southampton, who has an interest in nutrition and disease risk.

While there are different types of cholesterol in the blood, it is LDL (low density lipoprotein) cholesterol that is the harmful, or ‘bad’ cholesterol.

“It increases risk of heart disease because cholesterol can be deposited in the blood vessel wall and that starts the process of clogging up the arteries. It is very important for people who have high cholesterol to lower their levels,” he says.

Early intervention

However, while there is a focus on finding people with high cholesterol and trying to get them to lower it through lifestyle interventions or statin drugs, Professor Calder believes that younger people with lower cholesterol should also be aware of the potential future risk.

“Cholesterol levels go up as we age, so it makes good sense to catch people sooner and try to help them not go along the path of having high cholesterol,” he adds. “Tackling cholesterol earlier, before it has got too high, is very important.”

Lifestyle and dietary choices

Figures show that if you lower cholesterol by 10% in someone who is middle-aged, you can decrease the risk of heart disease in later life by 50%.

By highlighting the risk to people earlier in life, he says they can make lifestyle and dietary choices to reduce later risk.

Weight loss, reducing alcohol intake, doing more physical exercise and changing diet are all important. “There is a direct link between what people eat and their blood cholesterol concentration,” says Professor Calder.

Saturated fats, such as in animal fat, butter, high-fat cheese and palm oils can raise cholesterol. He suggests people switch to unsaturated fat by using margarine-type spreads, vegetable oils and eating more fibre.

Plant stanols in food

“In addition, people might want to think about plant stanols,” he says. “For example, Benecol® products contain plant stanols and these partly stop you taking up cholesterol into the body, and that can lower cholesterol.”

Plant stanols are found naturally in foods, so combined with other lifestyle interventions, food with added plant stanols can help people to take control of their cholesterol levels, one of the risk factors for coronary heart disease.

Figures show that if you lower cholesterol by 10% in someone who is middle-aged, you can decrease the risk of heart disease in later life by 50%.

Professor Philip Calder

Head of Human Development and Health, University of Southampton

WRITTEN BY Mark Nicholls

Early identification of elevated cholesterol levels in younger adults can have significant long-term benefits later in life.

Plant stanol ester has been shown to lower cholesterol. High cholesterol is a risk factor in the development of coronary heart disease. A daily intake of 1.5-2.4g of plant stanols has been shown to lower cholesterol by 7-10% in 2-3 weeks.

Benecol are proud supporters of HEART UK, helping people to know and understand their cholesterol levels.

Ways to better health for our one heart

The recent demise of high-profile public figures due to cardiovascular disease and some startling events on the sports field are unfortunate reminders that CVD is a disease without borders.

Cardiovascular disease (CVD) claims more lives globally than any other disease. However, 80% of premature heart attacks and strokes — responsible for a significant portion of the deaths and disabilities due to CVD — can be prevented. The causes and symptoms of CVD are multifaceted, and access to care remains variable.

Four avenues of heart health

To address healthcare access and implementation, the World Heart Vision 2030 focuses on equity, knowledge, innovation and climate policy as the four avenues for saving lives and averting the costs of inaction. Ensuring equity must cover healthy nutrition options, clean air and water, safe recreational spaces and

inclusion of data from clinical trials in under-served communities. Training, efficient task-shifting and applying research will help fill knowledge gaps. Improving data collection and upskilling in the use of digital tools along with wider access can help maximise innovation. With air pollution a risk factor for CVD, climate-savvy approaches in policies and initiatives entail curbing emissions across transport, energy, industry, agriculture and housing.

Breakthroughs and telehealth

High incidence and mortality should not eclipse the various improvements in cardiovascular care and CVD risk management. Statins and other therapies for treating high cholesterol effectively are more widely available.

A greater proportion of people with hypertension are being diagnosed and treated. Messages about lifestyle modifications resonate and encompass nutrition, exercise and tobacco cessation and target those with a genetic predisposition to heart ailments. In all these cases, improvements are not felt equally everywhere, and greater efforts are needed to tackle CVD in lowerresource settings.

New healthcare delivery mechanisms in telemedicine and other digital health interventions are equipping us to become empowered and stay in the know. Updates, reminders and heart activity readings are transmitted to millions of patients every day — often without a single trip to the doctor.

Prioritising heart health

We must widen measures to detect and prevent CVD, for example through screening and treatment access. Stronger coordination among health services for known CVD risk factors such as diabetes and hypertension is required, and taxes on products known to harm cardiovascular health should be implemented.

Science and sound health policies are allies for expanding cardiovascular care. Informed patients make for advocates of care that is available, affordable and timely. A holistic approach involving all sectors is our best bet for future cardiovascular health.

The World Heart Federation (WHF) represents the global cardiovascular community, uniting over 220 members such as heart foundations, scientific societies, patient organisations and civil society groups in more than 100 countries to share knowledge and advocate for heart health for everyone. Please visit worldheart.org

WRITTEN BY Daniel José Piñeiro President, World Heart Federation

Maintaining a healthy diet and making simple lifestyle changes can keep LDL-cholesterol levels low.

~Dr Peter Penson, Reader in Cardiovascular Pharmacology, Liverpool John Moores University; Medical Scientific & Research committee, HEART UK

A defibrillator is lifesaving equipment that gives an electric shock to the heart of someone experiencing ventricular fibrillation so that their natural pacemaker can reboot and restart in a normal rhythm.

Defibrillators will become increasingly common in workplace and home settings, says Jonathan Gilbrook, Managing Director of medical equipment firm, WEL Medical. Once, defibrillators could only be used by trained medical professionals, but technology now makes them simple to operate. Virtually anyone can use them to save a life.

How will the defibrillator market change in the next few years?

JG: In recent years, guideline changes regarding first aid in the workplace have seen defibrillators included in training courses. Plus, they’ve become increasingly visible in public locations. The Premier League have funded thousands of defibrillators, supplied free-of-charge to football clubs across the UK. Many of these have still not been claimed (visit premierleaguedefibs.org/ to claim one). We believe that demand for defibrillators in workplaces will continue to grow. As technological improvements make defibrillators smaller and less expensive, the biggest change in the next five years could be their appearance in homes.

How are you responding to this increase in acceptance of defibrillators?

JG: People want modern technology, simplicity of operation and value for money, so we’re about to introduce a more cost-effective defibrillator aimed at the layperson

and workplace. We also produce outdoor and indoor defibrillator storage cabinets which will soon be able to connect to the Internet of Things to allow people to remotely see that their defibrillator is being stored correctly and ready to save a life.

It’s reported that 80% of all out-of-hospital cardiac arrests happen in the home, so we’re working on a reasonable-cost defibrillator as part of our iPAD range for the domestic market. Our Brayden range of CPR (cardiopulmonary resuscitation) training manikins have been specifically designed to help laypersons understand and learn CPR.

What is being done to increase chances of survival for cardiac cases in the home?

JG: A challenge has been educating the public about defibrillators and CPR. We’ve been privileged to work with philanthropic and charitable organisations across the UK and Ireland that raise money to place defibrillators locally and provide CPR training.

In an emergency, people must know where defibrillators are located. The British Heart Foundation has a national database of public-access defibrillators — called The Circuit — linked to the Ambulance Services. If you’re responsible for a community defibrillator, or you have one in your workplace and are prepared to let the community use it, put it in an outdoor cabinet and register it with The Circuit (thecircuit.uk).

As the leading supplier for defibrillators in the UK, WEL Medical promotes the use of safe and accessible defibrillators to minimise harmful consequences during an emergency and strengthen the chain of survival.

With our vast range of defibrillators, cabinets and cases, CPR manikins and more, we are passionate about creating products that will benefit real people and real lives.

How more of us can now use defibrillators to save a life

INTERVIEW WITH Jonathan Gilbrook Managing Director, WEL Medical

WRITTEN BY Tony Greenway