If he had a choice, as a man, Prof Emeritus Dr Faiez Zannad would rather have colorectal cancer than heart failure.
The consultant cardiologist adds that if he was a woman, he’d rather have breast cancer than heart failure.
This is as the fatality rate for heart failure is not only higher than these two cancers, but is, in fact, higher than all but two cancers: lung cancer for men and ovarian cancer for women, he says.
Over 60 million people worldwide suffer from heart failure.
“Heart failure is the consequence of so many common diseases – obesity, diabetes, hypertension (high blood pressure), heart attacks – it is no wonder that it is extremely frequent.
“It is the common destiny of all heart diseases,” says the professor emeritus of Therapeutics at the University of Lorraine in France.
This also means that the number of heart failure cases is on an upward trend as the medical conditions that result in it are on the rise globally.
The ageing of societies worldwide is also a factor as heart failure is a condition that develops over time and usually strikes during the golden years.
In fact, it is the top reason for hospitalisation in those aged over 65.
However, Prof Emeritus Zannad notes that what is most alarming is not only the frequency of the disease, but also its deadliness.
“Half of patients with heart failure will eventually die within five years of their diagnosis,” he says.
Having to be hospitalised for this condition is one unfortunate predictor of death as about one-third of patients (32%) will die within a year of hospitalisation for heart failure.
“If the patient is lucky enough to be discharged from the hospital, they will leave with their heart weaker than before.
“Everything must be done to prevent hospitalisation for heart failure because it is very deadly and leaves you weaker,” he says.
Studies have found that the average survival time for patients decreases each time they have to be hospitalised; a sobering statistic considering that about one-quarter (24%) of heart failure patients are rehospitalised within a month of being discharged.
The good news for Malaysians is that only 1-2% of us have heart failure, according to consultant cardiologist Datuk Dr Azmee Mohd Ghazi.
The National Heart Institute (better known by its Bahasa Malaysia acronym IJN) Cardiology Department deputy head shares that the death rate in Malaysia is about 6% for those already warded in the hospital.
However, the fatality rate for heart failure patients within five years of diagnosis is similar to the global statistic of one in two patients at 48%, he notes.
Too little blood
Heart failure, also known as heart insufficiency, is essentially the inability of the heart to do its work properly.
There are two types of heart failure: with reduced ejection fraction (EF) and with preserved EF.
The heart’s EF refers to the amount of blood being pumped out of the heart – and to the rest of the body – when it contracts.
A normal EF, according to Prof Emeritus Zannad, is about 60%-70% (the remaining 40%-30% of blood remains in the heart).
In heart failure, the EF drops below 40%, and can dip as low as 15% to 20% in severe cases.
He explains: “The heart can fail either because it cannot pump enough blood into the circulation and the organs, or the heart cannot fill sufficiently.”
The former results in reduced EF, while the latter has preserved EF.
Heart failure with reduced EF can occur due to “an injured heart – after a myocardial infarction (heart attack), for example – or after a valve disease,” says Prof Emeritus Zannad.
In such cases, the heart muscles are just too weak to pump out sufficient blood to the rest of the body.
Meanwhile, “preserved EF is more often related to ageing and hypertension (high blood pressure),” he says.
In these cases, the heart has been working so hard against the blockages caused by plaque buildup in blood vessels over time or the high pressure within the blood vessels that its muscles have become overdeveloped – like a bodybuilder, he says.
As a result, the heart is now too stiff to relax properly and allow enough blood to enter it in order to be pumped out to the rest of the body.
So, even though the EF remains the same, the volume of blood going out has reduced.
In both cases, the final result is not only that the body’s organs are not getting enough blood with vital oxygen and nutrients, but that fluids in the body are also getting backed up as they are not being pumped away quickly enough.
This results in symptoms like fatigue, shortness of breath, irregular heart beats or palpitations, and coughing or wheezing.
These symptoms, Prof Emeritus Zannad points out, are common to many diseases, thus making heart failure difficult to diagnose.
He notes that the main sign of heart failure is congestion, which manifests as swollen legs due to the backed-up fluids (peripheral oedema) with reduced EF, and shortness of breath due to backed-up fluids in the lungs with preserved EF.
In addition to the rather high death rate associated with hospitalisation for heart failure patients, their quality of life in general also suffers.
As such, the major aims of treatment, according to Prof Emeritus Zannad, are to keep the patient out of the hospital, allow them to function as normally as possible and to improve their quality of life.
Dr Azmee shares that the treatment for heart failure patients with reduced EF is first and foremost, lifestyle changes.
These include limiting their fluid intake, eating a healthier diet, exercising, quitting smoking and limiting alcohol intake, among others.
Next comes the drugs.
He says that doctors usually choose one medication suitable for the patient from among three types of drugs known as angiotensin-converting enzyme (ACE) inhibitors, angiotensin-2 receptor blockers (ARBs) and angiotensin receptor neprilysin inhibitors (ARNIs).
Patients will also be prescribed a beta blocker and spironolactone, which is a mineralocorticoid receptor antagonist.
“These are the three main drugs we use for patients with heart failure,” he says.
“And of course, there are other medications for risk control.
“For example, if they have diabetes, we control their diabetes; if they have problems with cholesterol, we give them cholesterol medications.”
If the medications fail, then the next option would be the use of medical devices like a pacemaker, including one that provides cardiac resynchronisation therapy (CRT), or an implantable cardioverter defibrillator (ICD).
“And number four is advanced heart therapy, which is a transplant or a medical heart,” he says, adding that this therapy is only available in IJN for Malaysia.
Meanwhile, no specific drug has been shown to reduce the death rate of heart failure patients with preserved EF.
As such, treatment is usually tailored to the patient’s symptoms and related medical conditions (e.g. high blood pressure).
Prof Emeritus Zannad notes that despite the effectiveness and affordability of current heart failure drugs, many doctors are not prescribing them at optimal doses due to a fear of causing side effects.
“Doctors are concerned that some of these medications would induce hypotension (low blood pressure) and fainting, worsen the heart’s rhythm or increase potassium in the blood,” he says.
Therefore, safer and effective drugs are still needed for the treatment of heart failure.
This is where a class of drugs known as sodium-glucose cotransporter-2 (SGLT2) inhibitors may be of help.
A surprise discovery
Prof Emeritus Zannad shares that this class of drugs was originally developed to treat high glucose levels in diabetic patients.
“But curiously enough, we found out that this medication has other effects beyond controlling blood glucose.”
A systemic review of three large trials involving diabetic patients, published in The Lancet journal in 2018, found that “using SGLT2 inhibitors not only lowered glucose levels, but also dramatically decreased kidney failure (and) progression to haemodialysis, the rate of hospitalisation and death from heart failure, and the rate of stroke and myocardial infarction,” he shares.
Prof Emeritus Zannad and his colleagues from 20 countries across North and South America, Europe and Asia, specifically tested the SGLT2 inhibitor empagliflozin against a placebo in heart failure with reduced EF patients in a randomised phase 3 double-blind clinical trial called Emperor-Reduced, which began in 2017.
Published in the New England Journal of Medicine on Oct 8 (2020), the results were “very clear”, according to him.
He says: “In heart failure with reduced EF, where the patients may or may not have diabetes, there was a 25% decrease in the risk of the (study’s) primary endpoint of cardiovascular death and heart failure hospitalisation.
“There was a 30% decrease in the risk of recurrent hospitalisation, i.e. the total number of hospitalisations for heart failure.
“And this trial also looked at renal (kidney) outcomes – a very important complication of heart failure – and renal failure was decreased by 50%.”
He adds that this is the second such trial involving an SGLT2 inhibitor.
A similar trial using dapagliflozin was published last November (2019) in the same journal, showing similar results.
This, Prof Emeritus Zannad says, adds to the credence of their results.
In conclusion, he says that the addition of SGLT2 inhibitors to the current management plan for heart failure provides additional benefits for patients with reduced EF.
He also points out that: “Safety was excellent – these medications are very well-tolerated.
“If anything, they have fewer adverse effects than the usual medications we are currently using for heart failure.”
Both empagliflozin and dapagliflozin, along with canagliflozin, are currently available in Malaysia for the treatment of diabetes.
Boehringer Ingelheim Malaysia Medical head Dr Azhar Ahmad shares that the pharmaceutical company, which produces empagliflozin, aims to seek approval for the drug to be used in heart failure patients as soon as possible.
He estimates that it will take about 12 to 18 months to complete the process.
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