A hearty journey: mapping the advances of Chronic Heart Failure treatment
Dr Simon Cowap explores the advances in Chronic Heart Failure treatment, mapping our progress across the past 30 years and thinking forward to the future.
Even so, one area that does stand out to me is the treatment of heart failure. When I was a medical student I was taught quite a lot about the patho-physiology of heart failure. We learned about the Frank-Starling mechanism and the compensatory changes in heart failure affecting contractility, pre-load and afterload mediated by activation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS). But pretty much the only pharmacological treatment we had were diuretics and foxglove extract, and the prognosis for people with symptomatic heart failure was on a par with systemic malignancy.
My earliest encounter with CHF as an intern on the wards was with so called ‘cardiac cripples’. I remember one poor old chap on the 8th floor of Prince of Wales Hospital – really a diabetic ward – who just lay there, propped up on pillows, breathless at rest, day after day, night after night while we made him even more miserable by restricting his fluids and salt and gave him as much frusemide as his kidneys could stand. He was something of a permanent fixture; my recollection is that he was still there when I moved on to my next term, and I suspect he was discharged to the morgue.
As an RMO I did a lot of emergency department work. Pulmonary oedema was a common presentation between 2 and 6 a.m. At first it scared the crap out of me. These people were so breathless, so scared, so unwell, and at such imminent risk of dying. And it was my job to stop them dying! My own pulse, blood pressure and respiratory rate rose in tandem as I struggled to rapidly assess the situation, think what to do and insert the appropriate lines.
In the end I have to admit I came to almost enjoy managing acute pulmonary oedema. Mostly they did respond quite well to IV frusemide, nitrates, morphine, CPAP and the occasional inotrope infusion. Helping someone go from the distress of drowning in their own bodily fluids to resting peacefully a couple of hours later was really quite satisfying.
Interestingly enough, the therapy of acute pulmonary oedema has hardly changed since my emergency department days. But the general management of heart failure, at least the reduced ejection fraction type, has been transformed.
When I was a lad we avoided B blockers, thinking they would exacerbate CHF, and here they were saving lives.
Captopril, a drug developed from Brazilian viper venom, received FDA approval in 1981. It was the product of a deliberate attempt to target angiotensin converting enzyme, and built on work done in the 1960s to better understand the RAAS. The early ACE inhibitors were considered fearsome drugs, used only for hypertension, and only commenced in hospitals.
Then in 1991 the SOLVD trial showed adding enalapril to diuretics and digoxin significantly reduced mortality and hospitalisation in heart failure patients. Finally we had a treatment that worked! Eight years later, in 1999 the CIBIS-II trial proved that certain B blockers, in this instance bisoprolol, also reduced mortality and hospitalisation. When I was a lad we avoided B blockers, thinking they would exacerbate CHF, and here they were saving lives. Then CHARM in 2003 showed ARBs were an effective alternative to ACEI, and in 2011 EMPHASIS-HF added to earlier evidence that when added to ACEI and B Blockers, mineralocorticoid antagonists (spironolactone, eplenerone) further reduced hospitalisation and death. These agents were all great examples of rational drug development arising out of our physiological understanding of the RAAS.
And as if three major evidence based changes to CHF management in 20 years wasn’t enough, 2014 brought the results of the PARADIGH-HF trial showing that neprilysin inhibition, in conjunction with an ARB (so called ARNI therapy), caused a further reduction in hospitalisation and death when added to standard therapy. I was familiar with the RAAS from physiology lectures all those years ago, but what the ##**@ was neprilysin? Turns out it’s an enzyme that breaks down natriuretic peptides, which I’d vaguely heard of, and they undo the effects of an over activated RAAS.
So people graduating today have a much better chance of changing the future of their CHF patients, not just drying them out and providing symptomatic relief. On top of this there are fancy devices that make a difference, but ACEIs, ARBs, B Blockers and ARNIs can all be prescribed in general practice. It’s true that the HFpEF story is nowhere near so good, but diagnosing HFrEF is a whole lot less depressing than it used to be. That’s reason to celebrate, and to offer up three cheers to all those clever bastards in white coats who worked out the physiology of heart failure and designed drugs to manipulate it.
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Dr Simon Cowap MBBS (Hons), FRACGP
Simon is something of an accidental GP who likes to pretend he’s an artist trapped in a professional’s body. He dropped out of his first degree (arts) and went to London to play bass guitar in a band too musically challenged even for punks. Dropping back in to university, he subsequently also failed to complete a science degree and a Masters of philosophy. His remarkable lack of artistic success has been continued by the non-publication of his several novels. Somewhere along the line he did finish a medical degree. He still harbours dreams of literary success but his family have forbidden him to give up the day job.