Well over 500,000 people in Australia live with heart failure. Every day about 9 people die and 170 are hospitalised due to heart failure, according to the Heart Foundation, underscoring the need for effective prevention and management.
“It has a worse prognosis than most cancers,” says Professor Andrew Sindone, a cardiologist at Concord and Ryde Hospitals. “It is common. It’s expensive. And it’s the highest cause of hospitalisation in people aged over 65. And it makes people feel bad.”
When it comes to preventing heart failure, managing hypertension is key, Professor Sindone says.
Even if cardiac function is currently normal, treating hypertension helps prevent heart failure in the long term.
Left ventricular ejection fraction differentiates the three main types of heart failure. More than half of heart failure patients have preserved ejection fraction (HFpEF), with EF remaining greater than or equal to 50%.
Most advice about pharmacological management of heart failure focuses on those with systolic dysfunction, a left ventricular ejection fraction reduced to 40% or less (HFrEF).
For the grey area between HFpEF and HFrEF, patients with left ventricle EF of 40-49%, the European Society of Cardiology labeled this as a distinct entity in 2016: heart failure with mildly reduced ejection fraction (HFmrEF).
Treatment for HFrEF has changed considerably over the last decade. In 2013, ACE inhibitors were standard treatment for heart failure, along with beta blockers and mineralocorticoid receptor antagonists (MRAs)s.
Today there are four pillars of HFrEF therapy: combination angiotensin receptor blockers with neprilysin inhibitors, beta-blockers, MRAs and SGLT-2 inhibitors.
Every patient with HFrEF should be on all four treatments, Professor Sindone says. “This is the need for speed. We’ve really got to try and start these treatments early because people die fast.”
The ARNI has replaced ACE-inhibitors as first line therapy for heart failure.
This medication combines an angiotensin receptor blocker (ARB), plus a neprilysin (NEP) inhibitor that increases NT-proBNP levels to augment the vasodilatory effects.
The only ARNI currently available in Australia combines the ARB valsartan with the NEP inhibitor sacubitril.
The ARNI lowers blood pressure and sympathetic tone, via both natriuresis and diuresis. Compared to ARB alone, the sacubitril reduces aldosterone, fibrosis and left ventricular hypertrophy.
While ACE-inhibitors reduce mortality by about 20%, the ARNI reduces mortality by a further 16% over that, and further decreases hospitalisations as well.
A beta-blocker added to the first line management reduces mortality further, but can only be used in stable patients, Professor Sindone says.
Mineralocorticoid receptor antagonists like spironolactone add further protection, especially in severe heart failure or post-infarct.
The SGLT-2 inhibitors, initially indicated for diabetes, also reduce all-cause mortality and hospitalisations in heart failure patients, independent of their diabetic status.
Professor Sindone says the mechanism is multifactorial. “You lose pericardial fat so the heart is able to reach a better left ventricular end-diastolic diameter,” he says.
There is also loss of abdominal fat leading to less diaphragmatic compression, natriuresis and diuresis, and improved metabolism. SGLT-2 inhibitors also increase erythropoietin levels, decrease uric acid and are nephroprotective.
“SGLT-2 inhibitors are not diabetic medications. They are heart failure medications that have a side effect of lowering glucose,” Professor Sindone says.
Management of these patients focuses mostly on aggressive control of underlying risk factors.
In HFpEF, only SGLT-2 inhibitors significantly improve outcomes, reducing the combined risk of cardiovascular death or hospitalisation.
Spironolactone may offer some improvement in symptoms.
It is common for medications to follow a “start low, go slow” approach, but Professor Sindone warns that inadequately managed heart failure has up to a 50% five-year mortality rate. For this reason, cardiologists are embracing intensive guideline-directed medical therapy to reduce all-cause mortality.
This involves starting all four pillars of treatment at low doses in hospital and then uptitrating quickly over 2-4 weeks with weekly visits, Professor Sindone says.
If euvolaemic:
Angiotensin receptor neprolysin inhibitor and beta-blocker started immediately, then add spironolactone and SGLT-2 inhibitor as soon as possible.
If congested:
Angiotensin receptor neprolysin inhibitor and SGLT-2 inhibitor started immediately.Then add spironolactone as soon as possible, and the beta-blocker once euvolaemic.
The Heart Foundation guidelines recommend doubling the doses of heart failure medications every two weeks as tolerated, until the maximum tolerated dose is reached. The four medications should be initiated as soon as possible, without needing to achieve target dose of one before commencing the next.
With each initiation or dose increase, monitoring should include clinical review, blood pressure and heart rate measurements, serum potassium and renal function.
Ivabradine, a sinus node inhibitor, is added for patients in sinus rhythm with a heart rate over 77 beats per minute.
“Diuretics do improve symptoms but don’t improve survival,” Professor Sindone says. They have significant side effects including electrolyte abnormalities. If they must be used, Professor Sindone recommends a low dose loop diuretic, just enough to remove the excess fluid.
Digoxin similarly reduces symptoms but does not increase survival. Professor Sindone says it’s “an excellent seventh line medication.”
When prescribing medications for other conditions it’s crucial to “avoid drugs which can cause or precipitate heart failure,” he says, acknowledging that it’s a long list.
Iron deficiency
“Iron deficiency is one of the most important comorbidities,” Professor Sindone says. This is less about anaemia, and more about iron’s role in muscle function, mitochondrial function, and oxidative phosphorylation. He says that iron deficiency in heart failure follows different cutoffs to the rest of the population.
Infusion is recommended if:
In terms of nutriceuticals, Professor Sindone says the only one with evidence of benefit is the highly purified omega-3 ethyl esters. This offers only a small benefit and must be taken for 3.5 years before this is evident.
In short, we can’t. Professor Sindone says most heart failure is a serious irreversible condition that requires lifelong medication. “Unless a reversible cause has been found,” he says, stopping the medications will worsen symptoms and increase hospitalisation and death.
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