- Hello, welcome. This is Nicola Montana, professor of Internal Medicine at the University of Milan and we will talk about CIED infection. And we know that when a patient is dealing with CIED infection, there are emotion often involved. And this is true for all the clinical medicine, the faster the pathway to the solution, the better for the patients. However, this is not always the case. And to talk about this, I invited Mauro Biffi, director of the electrophysiology at the Sant'Orsola Hospital in Italy and Ignacio Ferreira, head of cardiology department of Vall d'Hebron Hospital in Spain to talk about their recent cases to illustrate this concept. Hello, both.

- Hi, Nicola.

- Hi.

- So Ignacio, let's start with you. You are a general cardiologist. So you don't implant, you don't extract. And so I'm curious to understand what makes you particularly interested in this topic.

- Yes, you are right, Nicola. I do not implant nor extract a device. Actually, I am involved in a heart team for the diagnosis and management of infected endocarditis. So I have experienced many patients with CIED infections and I can assure you that this is one of the most potentially complicated forms of endocarditis in case of the delay in the diagnosis and the treatment. So maybe perhaps for this, I'm so motivated trying to fill this gap in the healthcare and to help these patients or the management of this patient, yes.

- Yeah. Thank, you Ignacio. I totally agree with you. And it's very impactful for a patient when treatment is delayed really in any case. So Mauro, you have a particular case you wanted to share with us and could you tell more about this?

- Yes, going back to what Ignacio has told us, many times it's very difficult and intricated to reach a diagnosis of endocarditis in a CIED patient, especially when the endovascular portion of the system is involved. I remember a case of a gentleman that we implanted with a CRT-D unit. It's a sad case because of the longer time it took to get the right diagnosis and then to reach the proper treatment. This gentleman got the CRT-D but had significant comorbidities because he had Type 2 diabetes Mellitus and mildly reduced kidney function. So you can expect things were not so easy for him as he had also peripheral artery disease which is a quite common finding in a diabetic patient. He had a very successful CRT-D implant and improved heart failure status. So, he was really happy. But then around 15 months after implantation, he developed seizure symptoms because of a comorbidity and that was the peripheral artery disease coming to speak to the medical community because he got ulceration at two fingers on the right foot and so was seen very keenly on the cardiovascular surgery unit to get the proper treatment of this disease. This gentleman got percutaneous revascularization of the right leg and the topical treatment of the fingers. But then couple of weeks later, he developed feverish less than 35.5 degrees, so was seen at the emergency room because he felt something was not going right. And while he was evaluated, there was nothing on chest x-ray and was discharged on Amoxicillin Clavulanate oral treatment. He felt things were not improving. And after two weeks, he showed up again in the emergency room, this time with more consistent fever. And then the vascular surgeon decided that the four of the fingers were not going well and he had to undergo surgical toilet plus amputation of the distal part of the fingers and the patient was really disappointed because after having put his hope on improvement, he would really feel a failure. But then he was discharged home again with oral antibiotics plus gentamicin intramuscular. Three weeks, again, fever started to have bouts like night sweats, fever chills, shaking, and he came in with a clearly septical pattern of fever. At that point, it was admitted to the medical ward. But things worsened and he became really close to shock septic. Patient was admitted to the ICU and at that point things got really troublesome because heart failure came over. He developed almost acute renal insufficiency. And at that point, finally, the suspicion of endocarditis was raised and the echocardiography was taken and the vegetations were detected on the atrial side of the leads while blood culture showed methicillin-resistance to Staphylococcus aureus. So, the picture was clear. We were in front of a patient with septic stages due to CIED infection. And then we had to talk seriously to move fast to lead extraction. But the patient was so depressed that he felt, "Well, if there is risk, I'm going to die. And this will never solve and I'm bound to death." Although, it was a short time, relatively short time from implantation, so the extraction was really uneventful and easy in this specific case. But the course after the extraction was again dramatic because he had to undergo ultrafiltration due to multi organ failure related to the septic shock. Really, a horrible course. And he was discharged alive after 40 days, but almost deaf because of toxicity of vancomycin and diuretics. So, indeed, his quality of life was completely disrupted. Really sad because we saw this going on relentless. There was never a focus on the patient.

- Thank you very much, Mauro. As an internist, I would say that this is really the typical patient that we admit in our wards. So, multi-morbidity patients. And according to me, it sound really like this is a typical case of delay in the clinical pathway. What do you think?

- Absolutely. That is the most dramatic thing. You always find what you're looking for and if you don't think, imagine, what might be beyond a patient like this, you don't look and even a simple test is delayed like a echocardiography or blood culture.

- And this is the reason why we are here, to increase the awareness about a CIED infection. Another point is, where do patients present? Because this is also a very important point.

- Yeah, this is the most important point in my view because after the device has been implanted, rarely the patients show up to the outpatient device follow up clinic where the focus on this item is very high because we are well aware. So it's really important that the cardiology community and the internal medicine community are aware of this. But this should be in the hands of emergency room department, surgical department because this is a very broad concept. Every patient who has an implanted prosthesis, an implanted device, in case of fever, should be investigated for an infection related to the device. And this should be applied also in surgical departments, emergency room, and GPs as well. The general practitioner may be the first one giving an advice to the patient. Think that you have implanted foreign bodies in your vascular or in your hip or in your knee, wherever it is.

- Yeah, definitely. Thank you. Thank you, Mauro. And Ignacio, you said you have experienced delays in treatment as well in your hospital. Can you tell us a little bit more?

- Yes, yes. Let me tell you. This is a little different story. But yeah, it was not a problem with diagnosis but with the treatment. 69 years old male with hypertension, diabetes, and dyslipidemia. Most importantly, the patient had end stage renal disease that required regular hemodialysis. And because of this reason, the patient had arteriovenous fistula implanted and the patient also had been implanted a pacemaker eight years before because of atrioventricular block. Anyway, the patient started with fever and chills and he was admitted to a secondary regional centre. And yeah, initially they did very well. They took several blood cultures. Three of them were positive to a Staphylo aureus. And one day later, they performed a TEE which confirm large vegetation attached to the right ventricular lead of the pacemaker. So they started with triple intravenous antibiotic therapy. It is good, but they didn't contact any referral hospital for the whole system extraction. So three or four weeks later, they contacted our centre to transfer the patient. But because of persistent of the fever and the patient was finally admitted to our centre but in a critical condition. The whole system, it was removed and it was successful. But unfortunately, one day later, the patient died of complications peri-procedure, septic shock and massive thrombosis of the arteriovenous fistula. Yeah, and that was the devastating consequences of the delay in the referral in this case. Yes.

- So, a difference with the previous case. Here we are in front of the case in which the diagnosis was, let's say on time, but the treatment was delayed for the lack of knowledge of guidelines. So, and this is another. We talk at the beginning. You know, I started in my introduction talking about the mental condition of the patient and we know that in medicine, the delay of a direct diagnosis may impact mentally on the patient very badly. So how was the mental state of your patient when he arrived to you?

- In my case, yeah, the patient and the relatives were well-informed about the conditions and they were informed that they were to be transferred. The patient had to be transferred to another centre for the whole system removal. And yeah, that was okay. But the problem is that the relatives, and of course the patient, expected a good outcomes for the removal of the whole system. And yeah, it was very hard to inform them about the complications peri-procedural that finally caused the death of the patient. So Nicola, you can imagine that it was devastating in this case for the relatives, yes.

- And so this is a question for both of you regarding the case that you presented. What do you think the physician should have done differently? So Mauro, you first.

- Yeah, first thing is that we shall all remember that in the event of a CIED infection, 30 days mortality is 95% related to the medical condition that the patient has at his clinical presentation and not to the complication that might occur during lead extraction. So we must be very, very well aware that the time we are wasting in diagnosis is one of the key things that may promote a poor clinical outcome. We must do the best to our knowledge to rule out an endovascular CIED infection which has a tremendous mortality just like a massive valve endocarditis as Ignacio pointed out. So we must increase the awareness of every physician to raise the suspicion of the infection and do the right steps to confirm or rule out CIED infection. Increase awareness is key because you always find what you're looking for. And if you don't think, you don't look for. That is the first key thing. Then Ignacio, you should add something because diagnosis is not the only step we need to do.

- Yeah, that's true. I would say that once it's confirmed, the CIED infection, please refer immediately for complete removal of the whole system. And very important, I would also add, to bear in mind that the longer the delay in referral for system extraction, the higher the risk of the procedure. So you have to take this into account when informing the patient and the relatives about the potential risk of the procedure.

- So, thank you. So again, just to reinforce what you are just saying, so we have to really have in mind that giving clear and good information to the patient is very important, is crucial also for all the clinical, is a part, let's say, of our clinical management. Okay, so thank you. So do you have any other comment? Anything to add?

- You opened a very good point that is patient empowerment is the other side of the moon, the brightest one. Because if the patient is aware himself, then he can wake us before things get too worse. And that's probably the thing we are forgetting many times, to empower the patient and be an active part of the diagnostic pathway.

- I fully agree with Mauro.

- Exactly. We have to consider patient empowerment as a part of our clinical management. So, thank you very much Mauro and Ignacio. And so thank you for sharing with us your patient's history. And to summarise, I would say that first of all, CIED infection should be suspected by any specialist assessing a patient with fever or sign of infection. There is a simple rule of thumb. Infection plus device means extraction. So also in case of doubt, refer. And if refer, early. This is the only way the patient will have the best outcome and the most positive experience. If you would like to know more about what we as a physician can do to improve the care pathway for CIED infection patient, listen to our next podcast or visit the website, deviceinfection.com. Thank you very much.

- Thank you, Nicola.

- Thank you.