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Optimizing current and integrating new treatments to improve patient outcomes: experience from clinical practice (Part 1)
Burkert Pieske (Germany)
Burkert Pieske shares a clinical case of a patient who was referred to his clinical practice after failing to experience improvement in clinical symptoms or LVEF after two months of heart failure medication.
Optimizing current and integrating new treatments to improve patient outcomes: experience from clinical practice - University Professor Burkert Pieske
Dear colleagues, thank you for the opportunity to give you an example on integrating new treatments to improve outcomes. I am going to share with you a very recent case that I saw in our hospital this week. It is Sunday today, I guess so it was this week and I believe he was dismissed from the hospital yesterday.
These are my disclosures.
I am reporting on a so far healthy, sporty male, 65 years, physically active, reported that over the Christmas holiday he was still skiing. He is active, he is in Berlin, he has a private office as a paediatrician. There were no significant cardiovascular risk factors. He reported some respiratory infection five months ago and he experienced in January the first onset of heart failure-like symptoms which at that time were not yet correctly interpreted and they progressively increased in severity.
Last week he told me that active sports, for example are impossible – jogging, skiing are impossible at the moment and he feels really severely compromised.
Then during the initial outpatient work-up at the GP a new left bundle branch block was diagnosed. New we don’t know because the last ECG that was obtained in that healthy man was more than ten or 15 years ago, but at least left bundle branch block. This was the kick for the GP to send that person to a cardiologist and the outpatient echocardiogram then showed severely depressed left ventricular function with an ejection fraction of 30% and left ventricular dilatation.
Clinical case (cont.)
This is the ECG and you can see here the patient is in sinus rhythm and has a classical left bundle branch block with a QS duration of over 160 ms.
Clinical case (cont.)
This is the echocardiogram. I think it is from 19 May or it is from our department. This is the current status. We could confirm a dilative type of cardiomyopathy with reduced contractile function and speckle-tracking imaging here on the right-hand revealed mechanical dissynchrony and also strain rate analysis, significantly reduced longitudinal and also circumferential strain.
Clinical case (cont.)
Our diagnosis was in fact this is a now newly diagnosed dilative type of cardiomyopathy of unknown etiology. The diagnosis was already made three months ago in the outpatient cardiologist’s echocardiogram and the patient was put on heart failure medication. This was up-titrated on an outpatient basis over the last couple of months to what you see here; an ACE inhibitor, a beta blocker, spironolactone and torasemide.
Then, and this is typical for Berlin, the outpatient cardiologist referred the patient for coronary angiography to a peripheral hospital. They did coronary angiography and coronary artery disease was excluded and dilative cardiomyopathy was confirmed and the left ventricle filling pressure was elevated at 20 mmHg.
Clinical case (contd.)
Then they noticed that the symptoms did not really improve with the standard heart failure medication even at the doses that I could show you and then after an interval of two months, the patient was now referred to our institution for further etiological work-up which would consist of cardiac MRI and endomyocardial biopsy.
Remember there was this history of respiratory infection so is this viral myocarditis, is it a specific etiology of the cardiomyopathy and this was the reason for the referral of that patient this week to our hospital.
Clinical case (contd.)
I saw the patient I think on Tuesday for the first time. He did fairly well but he had this symptomatic heart failure. He was compensated so not severely volume overloaded, an ambulatory patient who came for the further etiological work-up, still New York Heart Association Class II to III, NTproBNP plasma levels quite elevated and the almost normal renal function in the so far healthy person.
Then we took some management decisions and I think these management decisions were in my view straightforward and remember, this was a paediatrician but still he completely understood what I was explaining to him. I told him ‘See, you are now on a full pharmacological heart failure therapy for the last four months. You felt perfectly fine half a year ago, you even did ski sports I think in Switzerland, I guess’.
Speaker: Why not?
Pieske: Why not – exactly – so I recommended him, irrespective of the outcome of the further work-up and we do not have the results yet because this is a current case, but this is my daily practice, I recommended him to change right away from an ACE inhibitor to an ARNE, LCZ.
Ruschitzka: Now comes friendly fire; Burkert, are you ready to take questions from us?
Pieske: Of course, always, especially from you Frank.
Ruschitzka: That’s good. Can you go one slide back? He was on which drugs already? That’s important. When we look at what we presented yesterday at the guidelines, this patient had, as you would expect at Burkert’s end, the perfect drugs out there.
He is an LBB patient who had ischaemics all ruled out, a candidate for CRT very soon, so now that is a patient if he is on an ACE and on a beta blocker you can consider spiro and then you can probably switch him.
What do you think, Michele? Is that a patient you would switch now?
Senni: Yes, I think this is a good patient, a typical patient that we saw in the Paradigm trial, the up-titration of all drugs, a good dosage of ACE inhibitor, a good dose of bisoprolol, but the NTproBNP remained high. think this is a truly good candidate for ARNE.
Ruschitzka: That is a picture perfect patient according to the new guidelines. I would say wonderful, so the question is, does he have to have spiro on board yes or no. The Americans may have a different take on that, but as we gain experience it’s fair enough that we wait for the patients to be adequately treated and then switch.
There are many questions to come – please go ahead.
Pieski: Just a comment. To me, this is a classical patient for spiro or eplerenone. I mean, ejection fraction 30%, symptomatic, I think this is a Class I for spiro. Renal function was good. Potassium – I didn’t show this – was good, so a classical case for spiro and I want to add something.
In my view, this is a healthy young man, a family, in the middle of his life; active – 65 – in the middle of his life. [Laughter] He comes from Japan I guess.
Ruschitzka: You have to understand, Burkert just became the father of twins, so that’s why.
Pieske: Anyway, I think this is a recent onset somehow for me of cardiomyopathy, whether it’s four months, six months when that has started we don’t know but I want to make sure this patient has everything on board to hold or maybe reverse the process because here we can get maximum benefit. I completely agree we have to take care of the elderly and the old, too but this patient is in full active life and we have to do everything and I think spiro is the backbone therapy for him in this scenario.
Ruschitzka: In Paradigm – I agree with you everything, but 50% of the patients didn’t have Class I and yet there was benefit. That is important just to note, but I agree the way we are moving forward, absolutely we are all in line.
There was a quick one, Burkert from Tiny.
Jaarsma: I just wanted to know, did you check if he took his medication?
Pieske: Oh yes, he took his medication. Yes, I checked this definitely and this is luckily a very reasonable guy, I am convinced he took his medication.
Ruschitzka: He is a paediatrician.
Jaarsma: Okay, sure.
Hobbs: Given that he is a young man, a very active young man, why not eplerenone rather than spironolactone?
Pieske: It is a good question. Referring to gynaecomastia as a side effect which is unwarranted and we have that less so with eplerenone, that is a good suggestion. This was the medication he came with. I didn’t switch; he was asymptomatic with it so I left it in.
Ruschitzka: He comes from England – price is not an issue there. [Laughter]
Hobbs: No, it’s quality. Quality is not an issue.
Ruschitzka: That’s good.
Pieske: As I said, he was referred for further etiological work, so what we did, and I started this week, I recommended him and he immediately agreed, we switched from an ACE inhibitor, the ramipril to LCZ. He was already on a reasonable dose of an ACE inhibitor, 5 mg twice a day, and he was haemodynamically completely stable; blood pressure 130, something like that so we didn’t start from the lowest dose, we started with 100 mg twice a day and we made sure that we had a 36-hour washout. This is on the ward, this is something also new and we have to really make sure we implement this and I myself took the ACE inhibitor pills out of his pill box for that evening, to be sure that he wouldn’t get it and then we had this 36-hour washout interval which is required when you switch from an ACE inhibitor to LCZ.
We would reschedule him. We dismissed him yesterday, I think cardiac MRI was done yesterday and Carsten Tschöpe is here - I don’t know whether he did the biopsy before he left for Florence so we don’t have these results, but irrespective of these results, we did the switch because this was an easy step.
We would reschedule him after one week to our outpatient clinic for assessment of blood pressure, wellbeing, renal function and electrolytes and we would then consider further up-titration to the target dose of 200 mg twice daily which I expect that he will tolerate.
Then with further decisions regarding, for example ICD or a CRT implantation or other specific therapies, we wait until we get the final results from the myocardial biopsy.
Ruschitzka: Burkert, may I ask a question? I have had my hands on LCZ now for a couple of months as well and I have learned a lot but you have to get a feel for a new drug. I don’t know how you feel, but I want to see it, I want to do it, I want to do it myself, see the patient and then I get some experience.
The blood pressure is a key issue for me. I have not seen any severe hypertension but I see the blood pressure dropping. There is some valsartan in it which is a powerful BP-lowering agent so I am careful with that. What was the standing blood pressure, remind me, of this patient, so that we are careful, particularly when we already go to the higher dose instead of the 50 bid, you went there because of the high ACE inhibitor background therapy to 100 bid?
Pieske: Frank, you raise a very important issue here, how would we take blood pressure, sitting, standing, so how are the standards?
I must admit in this patient I relied on the measurements that have been done by the nurses on the ward which were all in the range of 130. I am sure this was in a sitting position.
Ruschitzka: The nurse professor wants to say something to that.
Riley: I was actually going to say that one of the things you actually measured and you mentioned that you measured which I really think we shouldn’t underestimate is not just the systolic/diastolic but you measured the impact on the patient. You told us you measured their wellbeing and in my view, if the blood pressure is high enough for them to be functioning, they are not dizzy, they are cerebrating, they are urinating, etc then I think that’s hugely valuable and I like the way that you actually added that in to your parameters.
Pieske: Thank you for these comments and I think with hypotension I see two aspects that we should consider and Frank raised the third one and Jillian the fourth one, the wellbeing aspect.
First of course in a patient with severe advanced heart failure, blood pressure per se as a measurement is an issue and if the patient comes in with 100 and we increase the dose of whatever RAS inhibitor blood pressure will further drop or may further drop and this may become an issue – perfusion, etc. Even if the blood pressure is 130 or 140 and you lower it too fast and it gets to 120, the measurement doesn’t say anything, everything is fine, but the patient doesn’t feel good, he will not take the medication and this will become a problem then. Your points are very well taken.
Ruschitzka: Thank you, Burkert.
Pieske: This is the case. We had an internal discussion, for example when to implant a CRT device. Remember the patient had a left bundle branch block and I argued against CRT implantation in the next two or three weeks for two reasons. First I want to know the etiology as best I can and see whether we can provide a targeted therapy, be it anti-inflammatory whatsoever and see how ejection fraction evolves. Probably the patient will keep his left bundle branch block, but if the patient gets less symptomatic and ejection fraction increases say to 40%, maybe at the end the decision will be only a CRT device without ICD so we don’t know this yet.
My advice is he is not at high risk for arrhythmic events, wait a couple of weeks, see how the change in medication works, see what the etiological work-up brings to daylight and then decide.
Senni: Burkert, would you wait for two weeks or three months?
Pieske: You know, the three months, he was already on a good background medication so I wouldn’t wait for three months, but I think two weeks is too short.
Senni: Yes but now we are talking about optimal medical therapy and do you consider optimal medical therapy a therapy without LCZ?
Pieske: Wow! Now it gets really tricky. Michele Senni somehow he is always a little bit ahead of my thoughts but here you are right. Of course you could argue now we have optimised, now that is the time point where we have optimised the medical therapy and now we have to wait another three months.
I mean, since the patient at low risk for arrhythmic events, I could buy this notion. Say I see him in six or eight weeks and he is still symptomatic on an optimised dose of LCZ, maybe I would then go for CRT.
Ruschitzka: Just a reminder of yesterday’s guidelines which are now our guidelines for the next years, we put them on the same level so we kind of dodged this question a bit, whether we should have them all on LCZ first before we take the decision. Actually for me and I think we all agree, LCZ will now gradually become the optimised medical therapy and we will later on decide how we move it in the algorithm with more evidence to come.
But it was a wonderful, wonderful case Burkert.
Pieski: Thank you very much, Frank.
Ruschitzka: We continue some of the discussions now with Michele –