Mount Elizabeth Novena Specialist Centre
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Understanding Heart Failure Part 2
Management and Treatment
updated 26 July 2020
It is possible to live with Heart Failure. Lifestyle; diet and medication are all equally important. Early detection of build up of water is very important and this will help to keep you out of hospital.
Early Detection and Monitoring
Heart Failure causes water retention in the organs which drain back to the heart. These includes the.Lungs and Ankles, But rarely this may affect the Liver and Stomach. It may also reflect as a sudden weight gain of more than 1 kg per day. When this happens, patients should seek advice on the dosage of their medications especially the diuretics (water tablets).
Patients who have learnt how to manage their condition will usually adjust the dosage themselves - and it is not too hard to learn how to. Your doctor or nurse will be able to show you how to do it.
January 2018 82.4 kg February 2018 76.8 kg
Patient managed to reduce his weight from 82.4 kg to 76.8 kg over a period of 1 month; with water control and diuretics; note the progressive reduction in ankle swelling. This is not weight loss from fat or muscle; but salt and water loss.
(Please do not reproduce. Permission from patient only for this webpage)
Long Term Management
The Cardio-Renal Syndrome means that Heart Failure damages the Kidney and vice versa via the RAAS (Renin-Angiotensin Aldosterone System).
ACE inhibitor breakthrough
The discovery that blood pressure medicines such as Captopril could possibly block this harmful feedback loop was made in 1979. A major breakthrough was made in 1987 (CONSENSUS NEJM 1987), this showed that in patients with the most severe form of Heart Failure, Enalapril (which was a medication designed to lower blood pressure) could help Heart Failure patients live longer and better. This was a major breakthrough in what was until then a relentless disease with several failed therapies which only showed short term benefits. but was harmful in the longer term.
Shortly thereafter, in 1992, Captopril was found to improve survival in patients with poor Heart Function after a heart attack (SAVE NEJM 1992) and Enalapril could improve survival in patients with poor Heart Function without Heart Failure symptoms, regardless of their cause (SOLVD NEJM 1992).
Beta-blockers
Up till the late 1990's medical students were taught that beta-blockers should never be given in heart failure.The Swedes were the first to show beta-blockers improve survival in 1979 (Gothenburg Study, Karl Swedberg et al Lancet 1979). But this study was not taken seriously as they had only 24 patients randomised.
It took more than 10 years before doctors and pharmaceutical companies were brave enough to start a large enough study to look at its possible benefit. The first study to show survival benefit was with Carvedilol in 1996. Subsequently Bisoprolol and Metoprolol were also shown to have the same benefit, but unfortunately Bucindolol did not.
Spironolactone
This was an old medication that was repurposed to treat heart failure and was a pleasant surprise to all of us when the RALES study in 1999 showed a mortality benefit. This medication works by blocking part of the the RAAS.
Angiotensin Receptor Blockers (ARB)
This class of medication was developed as Angiotensin Converting Enzyme inhibitor (ACEi) were thought to provide incomplete RAAS blockade. In addition, some patients on ACEi developed a cough which does not cause harm but was troublesome. This class of medications were studied in several landmark studies such as Val-Heft and CHARM. These series of studies show that ARBs were as good as ACEi in treating of Heart Failure with an additional benefit in preventing hospital admissions.
However; addition of an ARB to an ACEi came with a slight benefit but at the expense of more renal complications.
Angiotensin Receptor Neprilysin Inhibitor "ARNI"
In 2015 ARNIs were the first drug to show a mortality benefit since 1999 in addition to standard therapy. The PARADIGM-HF study showed that it was superior to Enalapril (Enalapril was one of the first drugs to improve mortality),
Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors "SGLT"
SGLT's were originally desgined for diabetes, there was a serendipitous finding in the safety trial in 2015 which suggests that they prevent heart failure and death. Subsequent studies in patients without diabetes showed that these class of "diabetic medication" were also beneficial in heart and renal failure, This class of medication has since become standard treatment in heart failure regardless ofdiabetic status.
Technical Corner
This gets technical; please skip over if it's going to be "TLDR"
Water and Salt in Heart Failure
Our bodies are very efficient in retaining salt (Sodium Chloride or NaCl) as salt is naturally very hard to find in nature. Salt was also very expensive in ancient times up till the late 19th Century. In fact salt taxes were so lucrative that the East India Company derived 10% of their income from their monopoly and (excessive) taxation of the production and sale of salt in Colonial British India. This led to the famous "Salt March" in 1930 led by Mahatma Gandhi.
All salt ingested can only leave the body via the kidneys AND then only if the kidneys actively pumps out the salt. (Actually salt can also leave the body via sweating but as most of us are not physically active; the amount lost via sweating is relatively very little). So the more salt one ingests the harder the kidneys have to work to maintain the correct salt concentration.
To maintain the correct salt concentration; we will feel thirsty as well and drink more water to dilute the excess amount of salt we eat daily. This leads to increased total volume of water in the body and makes the heart work much harder to pump all these extra volume around.
In Heart Failure; the body thinks something is going wrong (correct) but tries to correct this by getting the kidney to slow down and keep the salt and water (wrong). This makes the water and salt retention worse. We now call this cardio-renal syndrome.
To break this cycle; we give patients "diurectics" or water tablets / injection to force the kidney to kick out the salt and water. Patients with good kidney function and who manages to control their salt and water intake; may be able to avoid taking these medications regularly. Although diuretics help get rid of the swelling and water in the lungs, they are harmful in the short term and need monitoring if taken at high doses for prolonged periods of time.
Diuretics
Water Tablets
These work by forcing your kidneys to lose salt (and hence water). It is very important to take them correctly as instructed. Side effects are mainly its effect on the kidney and Sodium / Potassium concentrations. They may also trigger gouty attacks.
Examples
Frusemide / Furosemide (Lasix)
Bumetamide (Burinex)
Metolazone
Hydrochlorothiazide
Beta Blockers
Blood Pressure / Heart Rate lowering
These were originally designed to slow down the heart and reduce blood pressure. They were found to help in heart failure by the Swedes in the late 1970's but was dismissed by the scientific community until their efficacy was proven in large clinical trials in the late 1990's.
Not all beta-blockers are the same and Bucindolol was shown to be ineffective in heart failure.
This class of medication may also be used to reduce heart rates or irregular heart rhythm. They may exacerbate pre-exisiting asthma.
Examples
Carvedilol (Dilatrend)
Bisoprolol (Concor)
Metoprolol Succinate (Toprol)*
Nevibolol (Nebilet)
*only Metoprolol Succinate is approved for heart failure and not Metoprolol Tartate.
Left Ventricle
Angiotension Converting Enzyme Inhibitors
"ACE" inhibitors
Originally derived from the poison of the Brazilian pit-viper. It was an excellent blood pressure medication that could lower blood pressure, protect the kidney and help the heart recover.
It was the first drug that was found to help patients with heart failure or a weak heart and after a heart attacks.
It may cause cough in ~ 20% of patients. while this is not a harmful side effect, some patients find this uncomfortable.
Regular monitoring of the kidneys are needed to monitor potassium levels after initiation. While it protects the kidneys it is often used in patients at risk of kidney failure.
Examples
Captopril (Capoten)
Enalapril (Vasotec)
Perindopril (Coversyl)
Lisinopril (Zestril)
Left Atrium
Figure 3
Figure 3
Angiotension Receptor Blockers
"ARB"
This drug was developed to circumvent the side effects of ACEi and also to see if a more complete inhibition of the RAAS system was possible and helpful.
It does not cause cough but like ACEi, regular monitoring of the kidneys are needed to monitor potassium levels after initiation. While it protects the kidneys it is often used in patients at risk of kidney failure.
Adding an ARB to ACEi was not shown to be beneficial in heart failure and led to higher rates of kidney complications especially hyperkalaemia (high potassium). However, some specialist may use this in combination in special cases with close monitoring.
It has been studied and shown to work in patients with heart failure and patients with early signs of kidney damage (microalbuminuria).
Examples
Losartan (Hyzaar)
Valsartan (Diovan)
Candesartan (Atacand)
Olmesartan (Olmetec)
Telmisartan (Micardis)
Fimasartan (Kanarb)
Figure 2
Angiotensin Receptor Neprilysin Inhibitor
"ARNI"
Researchers have been trying to increase the production of Brain Naturetic Peptide (BNP) in the heart but injecting it directly or by using a drug that blocks it from degradation. Initial attempts to inject it directly (ASCEND-HF) did not work and the oral version that was paired with an ACEi (OVERTURE) showed some modest morbidity benefit but an increased risk of a serious side effects called angioedema. Hence researchers were hesitant to try out this approach until PARADIGM-HF.
This class of drug is a 2 in 1 drug with a Neprilysin (Sacubitril) paired to an ARB (Valsartan). This is to allow Neprilysin to be delivered as an oral agent (instead of being injected).
Example (there is only one in this class)
Sacubitril-Valsartan (Entresto)
Mineralcorticoids
"MRA"
An old drug that was originally designed in 1953 as a blood pressure medication that works as a weak diuretic. It was later repurposed when it was found to prevent death in patients with heart failure reduced ejection fraction (HFrEF) in 1999; much later in 2014 it was studied in heart failure preserved ejection fraction (HFpEF); while the main study was equivocal, the sub-group analysis strongly suggests that it was beneficial.
It is also used in other conditions such as liver failure. Gynecomastia (swollen and painful breasts) is a possible troublesome but non-fatal side effect, the next generation drug, Eplerenone does not have this side effect.
Close monitoring of kidney function is important for this class of medication
Examples
Spironolactone (Aldactone)
Eplerenone (Inspra)
Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors
"SGLT"
This class of drug was originally designed for patients with diabetes. Derived from naturally occuring Phlorizin (found in apples), this was modified to stop glucose (sugar) from being reabsorbed and to allow sugar to be "lost" everytime someone passes urine. The first effective drug was described in 1999 in Japan.
This was the first class of diabetic medication that was able to show a reduction in death, heart attacks and heart failure in Type 2 Diabetes in a properly conducted double blind prospective study.
There is a risk of urine infection (especially in women) but this risk can be greatly reduced with good personal hygeine but if recurrent may have to be stopped.
Another risk is "euglycemic ketoacidosis" and this usually occurs when patient continues the medication despite fasting (e.g. for surgery) and this can be anticipated and prevented as we understand more about how this class of medication behaves.
Examples
Empagliflozin (Jardiance)
Dapagliflozin (Forxiga)
Canagliflozin (Invokana)