My name is Fernando Florido and I am a GP in the United Kingdom. In today’s episode I look at Chat GPT generated case of heart failure with co-morbidities to see how the NICE guidelines could apply to it.
I am not giving medical advice; this video is intended for health care professionals; it is only my interpretation of the guidelines and you must use your clinical judgement.
There is a YouTube version of this and other videos that you can access here:
· The NICE GP YouTube Channel: NICE GP - YouTube
You can download my summary of the guideline with additional information here:
· https://1drv.ms/b/s!AiVFJ_Uoigq0l3uRYZ7-U3R808gA?e=2LT5XI
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Transcript
Hello everyone and welcome. My name is Fernando Florido and I am a GP in the United Kingdom.
In today’s episode I look at the journey from diagnosis to treatment of a ChatGPT generated patient with heart failure and other co-morbidities to see how the NICE guidelines could be applied. Make sure that you stay for the whole episode because at the end, I am going to give you the pathophysiological reasons why ACEIs, ARBs, betablockers and MRA are so beneficial in heart failure, and I am sure that once you have understood it, you will never forget.
By the way, I am not giving medical advice; this is for health care professionals and it is only my interpretation of the guidelines so you must use your own clinical judgement.
If you want to download a copy of my summary of the NICE guidelines on Chronic heart failure, the link is in the episode description.
Remember that there is also a Youtube version of these episodes so have a look in the episode description.
Right, so let’s have a look at our fictitious patient:
- His Name is: John Smith
- His Age: 68
- Ethnicity: Caucasian
- Past Medical History includes: Obesity, Hypertension, Type 2 Diabetes, and Hyperlipidaemia
His Current Symptoms are:
- Shortness of breath on exertion and lying down
- a Persistent cough
- Fatigue and weakness
- Bilateral ankle swelling
- And The symptoms have been developing gradually over the last 4-6 months but recently he has noticed more rapid weight gain which could be from fluid retention
His usual medication is:
- Amlodipine 5 mg OD for hypertension
- Lisinopril 2.5 mg OD for hypertension
- Metformin 500 mg BD for type 2 diabetes and
- Atorvastatin 20 mg OD for hyperlipidaemia
So, we have a 65-year-old Caucasian male who presents with shortness of breath, fatigue, ankle swelling, and a persistent cough.
On examination we find the following:
His BMI is 34, so he is obese.
His Weight is 97 and John says that this is 4Kg more than his usual weight
His BP is 151/92 mmHg and
On auscultation, he has lung crackles. His heart sounds are regular with no murmurs, and his heart rate is 96 bpm. Palpation of the chest reveals a laterally displaced point of maximum impulse consistent with an enlarged ventricle.
His Oxygen saturation is 98%
And his Peak Flow is: 450 L/min (which is normal for his age and sex)
Abdomen showed no hepatomegaly and there is no raised JVP
He has Slight bilateral pitting ankle oedema
His Urinalysis and His Temperature are normal
Right, we have someone with lung crackles and a normal temperature and no other sings of infection, so it would be reasonable to suspect HF rather than bronchopneumonia. His main symptoms are suggestive of left sided heart failure although he also has some ankle oedema which is a possible symptom of right sided heart failure. However, he is also on amlodipine and at this stage we cannot be 100% sure of whether this is a side effect of his medication or secondary to heart failure.
Let’s remember that typical symptoms of left-sided heart failure include cool clammy skin, cyanosis, a laterally displaced point of maximum impulse consistent with an enlarged ventricle, lung crackles and a gallop rhythm. On the other hand, signs in right sided heart failure include an elevated JVP, ankle of leg oedema, ascites, hepatomegaly, and hepatojugular reflux. Signs of both left and right sided heart failure can be present at the same time.
In order to confirm the diagnosis of heart failure, we will need to measure the levels of the N-terminal pro-B-type natriuretic peptide, or BNP levels. In addition, and in order to exclude other diagnoses, NICE says that we should also arrange an ECG, a chest X-ray, especially as he has a persistent cough, other blood tests including full blood count, renal, liver, thyroid function, lipid profile, and HbA1c. Peak flow was normal for John but if we are in any doubt about a respiratory condition, we should also request spirometry testing.
Right, so we are going to send him off to have some tests. Should we be doing anything else in the meantime?
Well, if we feel that, clinically, he is having signs and symptoms of congestion and fluid retention, NICE says that we should offer diuretics for short term symptomatic relief. So, I would go for a loop diuretic, something like furosemide 20-80 mg daily depending on the severity of the symptoms and, obviously, the higher the dose, the closer that you will want to monitor him. But we should be seeing him again for a review within a day or two.
I am going to say that his symptoms and signs are significant so I will start him on furosemide 80mg daily and see him in a couple of days or sooner if he does not feel better.
Right, so, we organise the blood tests, to be done ideally the same day of next day and then we see him again to reassess and discuss the results.
At the next appointment, John states that his symptoms are better, his breathing is easier and his ability to do physical activities has also improved. On examination
His weight has gone down to 94.5 Kg but John says that his usual weight is around 93Kg
His BP is slightly better but still high at 144/87 mmHg. Remember that NICE says that for patients under the age of 80 their target BP should be below 140/90.
On auscultation, there are now minimal crackles at the lung bases and heart sounds are normal and in sinus rhythm with no murmurs. His heart rate is also lower at 80 bpm.
Oxygen saturation is 99% and
There is also less ankle swelling.
His Blood tests show that:
- His creatinine is 130 and his eGFR is 75 , so reasonable renal function
- His HbA1c is 60 or 8%
- He has a Normal FBC, LFT and TFTs
- His TC is 4.8, LDL 3.4, HDL 1 and TG 0.9
- And his BNP Level: 800 ng/litre
So, what do we say here?
We know that, if there is no heart failure, we would expect the BNP to be below 400 and therefore, with a raised BNP we can fairly confidently say that this is likely heart failure.
And because the symptoms have had an insidious onset over several months, we are going to say that he has chronic heart failure rather than anything acute that we should admit him to hospital for.
It's important to note that the BNP level does not differentiate between heart failure with reduced ejection fraction (or HFrEF) and heart failure with preserved ejection fraction (or HFpEF). We will need to organise an echocardiogram for this.
Also, we need to be aware that certain factors like obesity, African or African–Caribbean family background, and heart failure drugs can reduce BNP levels. Equally, they may be elevated for other reasons, for example, age over 70 years, ischaemia, tachycardia, hypoxaemia [including PE and COPD], renal failure, diabetes, or liver cirrhosis. John is both obese and has diabetes so he has factors that could be influencing his BNP in both directions.
His HbA1c is also high so we will need to intensify his diabetes treatment.
To know if his cholesterol levels on atorvastatin 20 mg are acceptable, we will need to look at his pre statin levels to be absolutely certain that he is on the right dose.
His other test results show that
- his ECG is normal with no signs of arrhythmia or ischaemia:
- his Chest X-ray shows: Mild pulmonary congestion and
- his Spirometry is also normal ruling out respiratory obstruction or restriction:
So, with these test results, we will discuss the diagnosis of heart failure with the patient and we will proceed with the referral for a echocardiogram. Because the BNP level is between 400 and 2000 ng/litre, he can have the echocardiogram withing 6 weeks. If it had been over 2000 ng/litre we would need to make urgent to be done within 2 weeks.
NICE also says that the purpose of the echocardiogram is to exclude valve disease, assess the ventricular function, and detect intracardiac shunts.
But now that we have a working diagnosis and that we are likely to be waiting for a few weeks for the echocardiogram, we need to start him on some further active treatment. And we have several issues with him:
1. Hypertension
2. Chronic heart failure
3. Diabetes
4. Lipids and prevention of CVD and
5. Obesity
So, let’s start with his hypertension. John is already on step 2 treatment, a combination of two drugs, amlodipine and lisinopril, none of which are at maximal doses. So, should we simply increase the doses of those drugs and then move to step 3 with 3 drugs if necessary? That would be the standard advice on the Hypertension guidelines. But not in his case.
The NICE guideline on hypertension says that for people with hypertension and CHF we must first follow the guidelines on CHF. So, if the HTA guidelines says that betablockers and spironolactone are considered at step 4 and the CHF guidelines say differently, we need to put the HTA guidelines to one side and give priority to the CHF guideline.
So, let’s have a look at the guidelines on CHF. What does it say about treatment? You may be familiar with the advice to give ACEIs, betablockers, mineralocorticoid receptor agonists or MRAs etc.
But these drugs are recommended in HFrEF and the first problem is that we do not know what type of heart failure this patient has. Is it HFrEF or is it HFpEF? Because, when it comes to treatment, the advice for each one can be different.
Could we assume that it is the most common type of heart failure? Unfortunately, that is not going to work because, at present, about 50% of patients with heart failure have HFpEF and the other 50% HFrEF.
By the way, remember that heart failure with preserved ejection fraction is characterised by a left ventricular ejection fraction of 50% or more. Heart failure with reduced ejection fraction has an ejection fraction of <40%. And there is now a third type, which NICE refers to as HF with mildly reduced EF which is when the ejection fraction is between 40 and 50%.
Right, so what do we do?
Well, we could look at the treatment of heart failure from 2 different perspectives:
· One, Symptomatic treatment
· And two, Preventative treatment
Symptomatic treatment addresses the congestive symptoms. And NICE says that we can give Diuretics for the relief of congestive symptoms and fluid retention in both types of HF. We will titrate them up and down according to need but, in particular, NICE says that in heart failure with preserved ejection fraction we will normally give no more than a low to medium dose of loop diuretics (for example, less than 80 mg furosemide per day) and refer if this is not enough.
The preventative treatment on the other hand is offered in order to reduce morbidity and mortality in the long run and it does not necessarily improve symptoms in the short term. These drugs are ACEIs or ARBs, betablockers, MRAs, ARNIs (which stands for Angiotensin Receptor-Neprilysin Inhibitors) and SGLT2 inhibitors. But all these drugs except the last one, SGLT2 inhibitors, confer these long-term benefits only to HFrEF, and we should not be pushing them if the patient has HFpEF.
Up to very recently, the same applied to SGLT2 inhibitors but, NICE changed the advice in June 2023 and now recommends dapagliflozin for all types of heart failure.
So, we conclude that not all drugs recommended for HF with reduced Ejection Fraction are recommended for HF with preserved Ejection Fraction. However, the opposite is true. General management for HFpEF can be applied to HFrEF.
So, let’s see what drug treatment NICE recommends for HFpEF, which is basically the recommendations for all types of heart failure, and how they apply to our patient:
· First, as we have already said, we can give low to medium doses of a loop diuretic, say furosemide 20-80 mg daily to relieve symptoms of fluid overload
o Our patient is on furosemide 80 mg daily and this has had a significant improvement in his symptoms. There are still some fine crackles in both lung fields and I may not rush to reduce the dose too quickly, although a careful reduction could be tried, for example to 60 mg daily advising the patient to increase the dose again if there are worsening of symptoms.
- Second, Dapagliflozin is an option for treating symptomatic chronic heart failure on the advice of a heart failure specialist only
- John still has some symptoms and this drug may be beneficial, but in order to give it for heart failure, we would need to get specialist advice. But we will touch on this a little later.
- Third, We will review drugs which may cause or worsen heart failure and stop them if appropriate- examples of these drugs would be both recreational drugs such as alcohol and cocaine as well as medication such as nonsteroidal anti-inflammatory drugs, beta-blockers, and calcium-channel blockers
- Our patient does not abuse alcohol and on our advice, he will cut down or even stop. He does not use other recreational drugs and he is not taking NSAIDs or betablockers. However, he is taking a calcium channel blocker, amlodipine. Is this going to be a problem?
- NICE says that (Calcium-channel blockers | Treatment summaries | BNF | NICE) calcium channel blockers, with the exception of amlodipine, should be avoided in heart failure as they can further depress cardiac function and exacerbate symptoms and they can also increase mortality after an MI in patients with left ventricular dysfunction and pulmonary congestion.
- So, with that said, our patient does not have to stop amlodipine, which is fortunate because he still needs to for his hypertension. There was a question mark as to whether some of the ankle oedema is secondary to amlodipine but for now, I would leave it as it is and reconsider this prescription later when more information about the patient’s condition is known.
- Number 4, we will consider An antiplatelet drug if there is atherosclerotic CVD (which is not always the case in HF)
- And John does not have this so he does not need aspirin or clopidogrel
- Number 5, we should give A statin if the patient is at risk of atherosclerotic CVD as per the NICE guidelines on CVD prevention
- John has already been found to be at high risk of CV disease and he is already on atorvastatin 20 mg daily. But the guidelines on prevention of CVD state that after statin therapy we should aim for a reduction in non-HDL cholesterol of 40% or more. His current lipids show a TC of 4.8, and an HDL of 1 so his non-HDL cholesterol is 3.8 (TC-HDL). Looking at his previous records we find that before the statin his TC was 5.9 and his HDL was 0.9, therefore then his non-HDL cholesterol was 5. 40% of 5 is 2 so his target non-HDL cholesterol should be 3 and instead it is 3.8. he is not hitting the target of a 40% reduction and I would therefore advise him to increase the dose of atorvastatin to 40 mg daily and recheck his lipids and LFTs again in 3 months.
· Number 6, part of the CHF management is the Management of other co-morbidities such as hypertension, diabetes, CHD, obesity, AF, COPD etc
o John has hypertension, obesity and type 2 diabetes as co-morbidities.
o Let’s look at the hypertension first. He is already on lisinopril and amlodipine and his BP is not down to target. We are worried that his amlodipine may be aggravating his ankle oedema, so I would probably elect not to increase the dose at this stage. However, It would make sense to increase the dose of lisinopril to, for example, 5mg OD, monitoring his BP and renal function. This way, if he has HFrEF, we are titrating one of the medicines that reduce mortality and morbidity in the long run. On the other hand, if he has HFpEF, we will still be managing it correctly by lowering his BP and improving one of his co-morbidities
o Let’s now look at his diabetes, which is not well controlled with metformin 500 mg BD. NICE says that the first step is always metformin and if metformin is not enough or not tolerated, we will assess the patient’s cardiovascular risk and status. And if the patient has heart failure, atherosclerotic CVD or is at risk of it, we should start and SGLT2 inhibitor.
o But you may be saying… did we not have to get a specialist opinion before giving an SGLT2 inhibitor for heart failure? And the answer is yes, if you are giving it for heart failure to someone without diabetes. But if the person has diabetes, it is the perfect opportunity to give it and treat both his diabetes and his heart failure, especially as it’s recommended for both HFrEF and HFpEF.
o But wait a minute, this patient is not on maximal doses of metformin. His eGFR is >60 so his dose could go from 500 mg BD to the maximum, double that, 1000 mg BD. Should we do that first? And my answer would be perhaps at some point. But I would not do this at this stage. Although HF is not a contraindication to metformin, the BNF says amongst other things that “the Manufacturer advises caution in chronic stable heart failure (and to monitor cardiac function), and avoid in conditions that can cause tissue hypoxia.” John’s heart failure is far from stable at the moment so I would not risk increasing the dose of metformin at this stage. With heart failure there may be a degree of tissue hypoxia which could put him at risk of the most feared side effect of metformin, lactic acidosis. In fact, some of you may be thinking that we should have stopped his metformin at the first visit, And perhaps that would have been a good option too, although you would be then be dealing with a whole lot of other issues secondary to uncontrolled hyperglycaemia. Because his oxygen saturation on the first visit was 98% and his condition had developed over many months, I wouldn’t view stopping metformin as an urgent matter. Of course, if he had been truly unwell and hypoxic, that would have been the right thing to do.
o Another co-morbidity to consider would be his obesity. So, lifestyle advice, maybe orlistat and further referral for support will be indicated at some point. But he has enough on his plate now, so I would park this for the time being and revisit it in future.
- Finally, in HFpEF NICE says that we need to refer if there is poor response to diuretic therapy or if valve disease is discovered.
- But John has responded well to furosemide and auscultation of his heart did not detect any murmurs, so hopefully there will not be anything significant there. But we will have to wait for the echocardiogram report to be completely sure.
So, in summary:
· We will continue furosemide either the same dose of 80 mg daily or more likely cautiously reducing it to 40-60 mg according to our clinical judgement, especially considering that
· We are going to start an SGLT2 inhibitor, which also have a diuretic effect. Something like for example dapagliflozin 10 mg daily would be good.
· We will also continue amlodipine 5 mg OD and
· We will increase atorvastatin to 40 mg daily and
· We will increase lisinopril to 5 mg, monitoring his renal function and
· We will advise him to continue monitoring his weight and to let us know any concerns
I would suggest that we see him possibly 7-10 days later to review his progress and medication but we will also give him very careful safety-netting advice to come sooner if anything does not go to plan
Ok, so, When we see him next, John is feeling very much better, his breathing has improved as well as his tolerance to exercise.
His weight is now 92.8 which is more like his usual weight.
BP is 138/82 mmHg
On auscultation, his chest is clear and his heart sounds are normal
Oxygen saturation is 99%
Ankle oedema has all but disappeared.
And His renal function has remained reasonably stable although since increasing lisinopril, his eGFR has decreased from 75 to 69 and his creatinine has risen from 130 to 143
We have also received his Echocardiogram Result which shows:
- that There is evidence of left ventricular hypertrophy, possibly the effect of prolonged hypertension
-Right ventricular function and cardiac valves are normal and there are no cardiac shunts but
- he has a Left ventricular ejection fraction (LVEF) of 35%, so, being <40%, he has HFrEF
So let’s have a look at the guideline for this. For the treatment of heart failure with reduced ejection fraction NICE says that:
1. for First-line Treatment we need to give the maximal tolerated doses of:
1. An ACE inhibitor and
2. A beta-blocker licensed for heart failure
· The beta-blockers licensed for heart failure in the UK are bisoprolol, carvedilol, and nebivolol.
· And We will not withhold betablockers solely based on age or the presence of peripheral vascular disease, erectile dysfunction, diabetes, interstitial pulmonary disease, or COPD.
3. NICE says that we should use our clinical judgement when deciding which drug to start first.
4. But we will not give an ACE inhibitor if there is haemodynamically significant valve disease until the valve disease has been assessed by a specialist.
5. And We will give an ARB licensed for heart failure if there are side effects with ACE inhibitors.
· ARB licensed for heart failure in the UK are Candesartan, losartan, and valsartan.
6. If there are persistent symptoms, we will then give a mineralocorticoid receptor antagonist (or MRA), such as spironolactone or eplerenone, in addition to an ACE inhibitor (or ARB) and beta-blocker
OK, so John is already on lisinopril so we should start him on a betablocker next, for example bisoprolol starting at 1.25 mg daily increasing gradually according to the BNF. Also, we should also gradually increase his lisinopril and, as the blood pressure drops, it is likely that we will need to discontinue amlodipine. We will use our clinical judgement as to how quickly the titration of both lisinopril and bisoprolol is but NICE recommends doing so at short intervals (for example, every 2 weeks) until the target or maximum tolerated dose of both drugs is reached.
But we have noticed that both John’s creatinine and eGFR have deteriorated since we increased the dose of lisinopril. Is that going to be a problem?
NICE says that we only need to worry and take further action if the creatinine level increases by more than 20% or the eGFR falls more than 15%.
John’s creatinine has increased by 10% and his eGFR has only decreased by about 8% so we should not be too concerned but we will keep monitoring it.
In terms of monitoring, we will do a full clinical assessment at every review, measuring his BP and renal function, including sodium and potassium levels, before and 1 to 2 weeks after starting the drugs, and after each dose increment. We will also assess heart rate when giving betablockers.
And we will not forget to monitor his HbA1c and his lipids after the management changes.
NICE says that once the target or maximum tolerated dose is reached, we will monitor the treatment monthly for 3 months and then at least every 6 months, and at any time if he becomes acutely unwell.
NICE says that we should monitor BNP levels only if:
· The patient is under 75
· there is heart failure with reduced ejection fraction and
· the eGFR is above 60.
So, we should monitor John’s BNP levels which will help track his response to treatment.
A follow-up echocardiogram may be performed from time to time to assess if there have been changes in the left ventricular ejection fraction
If his symptoms do not improve with the initial treatment with an ACEI or ARB and a betablocker, We will consider the addition of Mineralocorticoid Receptor Antagonists (MRA), for example, something like spironolactone 25mg daily increasing to 50 mg, according to response.
I am obviously describing the steps that we would have to follow according to the guidelines but, in practice, we would also refer him to see a cardiologist, early on, to ensure that he gets specialist advice and that his treatment is fully optimised
For your information, NICE recommends that the following drugs should be initiated by a Specialist only
· Ivabradine
· Sacubitril valsartan
· Hydralazine in combination with nitrate
· Digoxin
Other General Recommendations for John will include:
1. an annual flu vaccination and a one-time pneumococcal vaccination
3. Advise to stop Smoking and reduce alcohol to recommended levels and
6. in terms of Sodium and Fluid Consumption:
- we will not routinely restrict them but will enquire about his intake and.
- If John experiences dilutional hyponatremia, fluid restriction may be advised and
- If John has high levels of salt and/or fluid consumption, he will be encouraged to reduce.
- And Finally, we will advise him to avoid salt substitutes containing potassium.
Right, so we will make this the end of this patient’s journey with us.
But, as promised, let’s talk pathophysiology and the reason why ACEIs, ARBs, MRAs and betablockers have long term benefits in heart failure.
And we will start by saying that Heart failure with reduced ejection fraction, even in its early subclinical stages, leads to reduced organ perfusion, precisely because of the reduced ejection fraction. To compensate for this, the body triggers a response that stimulates the sympathetic system and the RAAS. Stimulation of the sympathetic system produces vasoconstriction and faster and stronger myocardial contractions, whilst the stimulation of the RAAS causes vasoconstriction due to the angiotensin effect and increased fluid and sodium reabsorption due to the aldosterone effect, both of which lead to an elevated blood pressure. Although these mechanisms may initially improve tissue perfusion, they also have a remodelling effect on the heart, eventually inducing harmful structural changes which exacerbate heart failure over time.
The mentioned medications act through different pathways to reduce the heart's workload, enhance cardiac output, and counteract the detrimental effects of the neurohormonal activation. The betablockers do so by blocking the sympathetic system and the ACEIs, ARBs and MRAs by blocking different sections of the RAAS. They are all essential components of evidence-based heart failure management, reducing hospitalisations and mortality.
Given that one of the problems of the RAAS is fluid and sodium retention, you might wonder why patients aren't routinely advised to reduce their fluid and sodium intake. Well, in this world of evidence-based medicine the answer is easy. The reason is that there is currently no research evidence supporting this advice. While it might seem intuitively reasonable, we should refrain from recommending it unless there is concrete evidence indicating that the patient's salt consumption or fluid intake is excessive.
But remember that this is only my interpretation of the guidelines.
We have come to the end of this episode. I hope that you have found it useful. Thank you for listening and good-bye
