Heart Failure

Summary — Heart failure is a field in which stem cell research has progressed to relatively large randomised studies. The US POSEIDON study (2012, 30 patients) compared autologous and allogeneic mesenchymal stem cells, confirmed the safety of both, and reported changes in scar size and some functional measures. The DREAM-HF study of more than 500 patients (2023) did not meet its primary outcome but reported some secondary outcomes, such as heart attack and stroke, and results in a subgroup with high inflammation. In Japan, cardiac regenerative medicine research has continued, centred on Osaka University.

What is heart failure?

Heart failure is a state in which the heart cannot pump as much blood as the body needs, or cannot fill properly. Rather than a single disease, it is the result of various heart conditions progressing — myocardial infarction, hypertension, cardiomyopathy, valve disease, arrhythmias and others. Typical symptoms are breathlessness, fatigue, swollen legs and difficulty breathing when lying down. It is increasing with population ageing and frequently leads to hospital admission and readmission.

It is classified by left ventricular ejection fraction (LVEF), a measure of pumping function, into heart failure with reduced and with preserved ejection fraction, among others, and treatment differs accordingly. Stem cell research has mainly targeted heart failure with reduced ejection fraction caused by damage to heart muscle, for example after a heart attack.

Current standard treatment

In heart failure with reduced ejection fraction, standard care combines several drug classes — beta-blockers, renin–angiotensin system inhibitors, mineralocorticoid receptor antagonists, SGLT2 inhibitors and others — whose benefits on survival and hospitalisation have been confirmed in large studies. Implantable defibrillators, cardiac resynchronisation therapy, left ventricular assist devices and heart transplantation are considered where needed. But there is still no treatment that reverses heart muscle once it has been damaged and scarred, which is why research into regenerating the heart with cells has been active since the early 2000s.

Why stem cells are studied

Early studies hoped that infused cells would become new heart muscle cells and fill damaged areas. Later research led many to conclude that most effects arise indirectly from factors the cells secrete — reducing inflammation, promoting new blood vessels, limiting scar formation and protecting surviving heart muscle cells. Mesenchymal stem cells also attracted attention because they provoke little immune response, so donor (allogeneic) cells can be prepared in advance.

Reported research findings

① POSEIDON (University of Miami and others, US, 2012) — 30 patients with ischaemic cardiomyopathy after heart attack were randomised to autologous mesenchymal stem cells from their own bone marrow or allogeneic donor cells, injected at several sites into the inner heart wall by catheter; three doses were also compared. The main aim was to compare safety, and no worrying immune reactions or serious arrhythmias were reported with allogeneic cells. Scar size measured by CT decreased with both approaches, and six-minute walk distance and quality-of-life scores improved in some groups. Left ventricular ejection fraction, however, did not change significantly. Published in JAMA, the study is often cited as evidence for the safety of allogeneic cells.

② DREAM-HF (2023) — a large randomised study of more than 500 patients with chronic heart failure with reduced ejection fraction, comparing injection of allogeneic mesenchymal precursor cells into the inner heart wall with a sham procedure. There was no significant difference between groups on the primary outcome, recurrent events such as hospitalisation for worsening heart failure. In secondary and exploratory analyses, the investigators reported fewer heart attacks and strokes in the cell group and a better trend in outcomes such as cardiovascular death among patients with high blood levels of inflammation. These were presented as hypotheses needing further study.

Research in Japan

In Japan, cardiac regenerative medicine research has continued, centred on an Osaka University team. An approach that forms the patient's own skeletal myoblasts from thigh muscle into sheets and attaches them to the heart surface received conditional, time-limited approval for severe heart failure in 2015; this product uses muscle cells, not stem cells. The team has since carried out clinical research transplanting sheets of heart muscle cells made from iPS cells into patients with ischaemic cardiomyopathy.

Safety and open questions

So far, catheter injection of cells into the heart has generally been performed safely at experienced institutions, but the procedure itself carries risks of arrhythmia and cardiac injury that require careful management. For stem cell research in heart failure to advance, studies are needed that define in advance which patients are most likely to benefit and test whether there is added benefit on top of standard drug therapy. A review of the clinical use of mesenchymal stromal cells also names cell quality and potency measurement as key challenges.

How results are measured in heart failure research

Heart failure symptoms are classified into New York Heart Association (NYHA) classes 1–4 according to how breathless people become with everyday activity. Studies use left ventricular ejection fraction and heart size measured by echocardiography or MRI, six-minute walk distance, blood NT-proBNP levels and questionnaires such as the Minnesota Living with Heart Failure Questionnaire. In large studies, events such as heart failure hospitalisation and cardiovascular death are the primary outcomes.

The above summarises results reported in published papers and public-agency materials. University and institute names are given to identify research sources, not to introduce or recommend any medical institution. Reported results do not mean the same effect for everyone, and the suitability of any treatment is decided by the medical team.

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