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A bright future ahead for cardiology

By Dawn O'Shea - 13th May 2024

Anatomy of Human Heart on science background. 3d render

Prof Thomas Lüscher, European Society of Cardiology President-elect, addresses the recent inaugural Dublin Heart Summit

One-shot treatments, new target organs and gene therapies are on the way for cardiology, according to the President-elect of the European Cardiology Society. Speaking at the inaugural Dublin Heart Summit hosted by Mater Private Network at the Royal College of Surgeons in Ireland recently, Prof Thomas Lüscher said the future looks bright for cardiovascular medicine.

Prof Lüscher is currently Director of Research, Education and Development and consultant cardiologist at the Royal Brompton and Harefield Hospitals and is Professor of Cardiology at both Imperial College and King’s College London. He is among the top 0.1 per cent most cited scientists in the world.

He told the conference that the specialty has come a long way, pointing, in particular, to the significant decrease in acute coronary syndrome (ACS) mortality rates. In the 1950s, mortality rates for ACS were almost 50 per cent, but advances in knowledge and therapies have seen that rate decline to 10 per cent. Unfortunately, that decline has stagnated for the last 15 years, but novel therapeutic targets signal dramatic improvements ahead.

Inflammation

Cardiogenic shock has long been associated with poorer survival in ACS. Clinical trials have shown that in haemodynamically stable patients with acute myocardial infarction (MI), primary coronary intervention (PCI) improves survival. However, this benefit has not materialised in patients with cardiogenic shock. Extracorporeal membrane oxygenation (ECMO) has also failed to deliver real improvements in these patients, while intravascular micro-axial left ventricular assist devices have been shown to actually increase mortality in this patient population.

Prof Lüscher said “a paradigm shift” is underway and more attention is now being brought to bear on the inflammation and neuro-hormonal activation that drives clinical deterioration in patients with cardiogenic shock.

A number of proof-of-concept trials are currently underway looking at the effect of anti-inflammatory and immunosuppressive therapies in ACS.

He highlighted work involving dipeptidyl-peptidase-3 (DPP3), an enzyme central to the processes of pain signalling, inflammation, and oxidative stress. It is involved in the degradation of angiotensin II which disturbs peripheral blood pressure regulation and compromises left ventricular function. Persistently elevated DPP3 concentrations are predictive of cardiogenic shock and mortality in ACS. It has been shown that inhibition of DPP3 in a mouse model resulted in a prompt return to normal cardiac function and haemodynamics. Prof Lüscher expects DPP3-targeted therapies for ACS to enter clinical trials shortly.

He also suggests that a cure is within reach for some cardiovascular conditions. CRISPR has opened the door to a world of possibilities. Trials are already underway in a number of conditions. For example, NTLA-2001 is a new CRISPR-Cas9–based in vivo gene-editing therapy for ATTR amyloidosis. It inactivates the TTR gene in liver cells to prevent the production of misfolded transthyretin (TTR) protein.

Could CRISPR provide a cure for atherosclerosis? A recent study in primates demonstrated that CRISPR base editors achieved a near-complete knockdown of PCSK9 in the liver after a single infusion, with concomitant reductions in blood levels of PCSK9 and low-density lipoprotein cholesterol of approximately 90 and 60 per cent, respectively. All of these changes remained stable for at least eight months after a single-dose treatment.

If the treatment proves as successful in humans, “we can shut down most of the cath labs in the future,” Prof Lüscher said.

“With a statin or an antihypertensive drug, you take your tablets every day. With the antibodies it’s actually twice a month or once a month. Now with the [small interfering RNA products] it’s twice a year, but in the long-term, it will be once in a lifetime. We’ll be moving from treatment to cure in the future,” he said.

A tale of two diseases

As we await these new therapies, there is still a need to optimise existing treatment options for some patients, particularly for women with coronary artery disease (CAD).

In a second presentation, Dr Róisín Colleran, consultant interventional cardiologist at Mater Private Network in Dublin, pointed out that women are currently less likely to receive  primary or secondary prevention, and women are under-represented in clinical trials. Moreover, there has been a stagnation in the reduction of CVD burden in women over the last decade. Rates of deaths from cardiovascular disease in women in the US and Canada have started to increase in recent years.

Dr Colleran said that while there are many similarities between men and women with CVD, there are specific considerations that should be kept in mind when treating women.

Traditional cardiovascular risk factors can affect women differently, she said. For example, hypertension tends to cause more left ventricular hypertrophy (LVH) and dystonic dysfunction, in women. There are also sex-specific risk factors to consider, including premature menopause, polycystic ovary disease and gestational diabetes.

Presentation also differs between men and women. While chest pain is the most common presentation of ACS, women tend to have higher rates of less typical symptoms, such as dizziness, nausea or vomiting, jaw or neck pain, or shortness of breath.

Dr Colleran reported that myocardial infarction with no obstructive coronary artery disease (MINOCA) is more common in females. There are a number of causes of MINOCA and she highlighted the importance of following the ESC’s MINOCA diagnostic algorithm.

Spontaneous coronary artery dissection (SCAD) is also more common in women, with an estimated 90 per cent of cases occurring in women aged 47 to 53 years. It has been suggested that SCAD may account for up to a third of myocardial infarctions in women under 50.

It typically presents as a STEMI or non-STEMI, although troponin is negative in about 27 per cent of cases. It can occur in any coronary artery, but the left anterior descending artery (LAD) and its branches are most commonly affected.

The gold standard of diagnosis is angiography with or without intravascular imaging. CT coronary angiography (CTCA) can also be helpful.

In relation to the acute management of SCAD, less is more, Dr Colleran said.

“We interventional cardiologists like to fix narrowings when we find them in coronary arteries, but in this instance, it’s not generally a good idea, because we can do a lot more harm. We know that PCI is associated with worse short- and long-term outcomes in SCAD versus atherosclerotic disease. More than 80 per cent of lesions heal successfully over time and can probably be successfully treated medically,” she said.

“In the 2023 ESC guidelines, PCI is recommended only if the patient has ongoing symptoms and signs of myocardial ischaemia with a large area of myocardium in jeopardy and reduced antegrade flow. So if the flow is normal, generally it’s recommended to get out of there,” she said.

“In terms of long-term management, again we don’t know that much. There are no trials, but it’s recommended to treat chronic cardiac chest pain with antianginal therapy to prevent recurrence. Beta blockers have been shown, in observational studies, to prevent recurrence, and then assess for extra coronary vascular abnormalities, for example fibromuscular dysplasia,” she added.

Save the date

In total, the day-long Dublin Heart Summit featured 10 presentations on a wide range of topics including an update on interventions for tricuspid regurgitation, catheter ablation for atrial fibrillation, and the role of cardiac MRI in clinical practice.

Speakers included Prof Borja Ibanez from the Spanish National Centre for Cardiovascular Research and Dr Rasha Al-Lamee, an interventional cardiology consultant at Imperial College Healthcare NHS Trust in London. The inaugural event recorded  almost 400 attendees in person and online combined and a recording of the meeting is available on the MedCafe and Mater Private Network websites.

To view a highlights video of the event please click here

The date for the next Dublin Heart Summit has already been set – 12 April 2025.

This report was funded by Mater Private Network

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