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Management of Severe Right Heart Failure in PTE Patients
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Dr. Marc de Perrot presents "Management of Severe Right Heart Failure in PTE Patients", recorded live at the UC San Diego Health Sulpizio Cardiovascular Center National Proceedings: CTEPH 2017.

This transcript is software driven, please understand there may be errors.  Should any inaccuracies or omissions be found, please notify for correction.

Management of Severe Right Heart Failure in PTE Patients

Good afternoon, I hope you had a good lunch, and I have the difficult task to keep you all awake here. I'm gonna speak about the right heart failure, and I have a number of pictures, and I'll speak a bit more about ECMO, but I especially would like to thank Bill O'Jay and the whole team for the invitation and the privilege to be here, to be speaking with you, and to see many colleagues and friends today and tomorrow.

So, just some honorarium from Bayer as a disclosure.

So as you all know well, the outcome of pulmonary endarterectomy are currently excellent, we still have an operative mortality of less than 5% in the vast majority of the centers. Interestingly, despite the long cardiopulmonary bypass and the deep hypothermia, the majority of the patients don't even need any blood transfusion. Deep hypothermia has been shown to be safe with a circulatory arrest of 18 to 20 degrees, and the outcomes in the long term are excellent.

The part that remains difficult is the dysfunction of the right ventricular [inaudible 00:01:08], it's still a major risk factor for the surgery. This is the study from Vienna published last year. When they looked at the whole experience, about 20 years with a bit over 200 patients, in-hospital mortality of 6.5 percent of all ... that improved of other years, but the main cause of this was right heart failure in more than half of the patients. Under risk factor for 30-day mortality was elevated pre-operative pulmonary vascular resistance, New York Health Association functional class 4, and low cardiac index. All factors related to right ventricular failure has risk factor from pre-operative mortality here.

This is also seen in this international registry where there was a fairly good correlation between pulmonary vascular resistance pre-operatively and the operative mortality, with operative mortality going up to 10% when PVR was greater than twelve-hundred Dynes.

However, with increasing experience, as in San Diego, they have shown that over the latest part of the cohort, the operative mortality for PVR greater than 1000 Dynes, the mortality decreased by over half to less than 5% between 2006 and 2010. And also, in the lower-risk category, the operative mortality improved, but to a lesser degree.

And this was despite the fact that more patients with distal disease or segmental disease or subsegmental disease have the surgery. So, improved mortality despite potentially more distal disease.

And they have refined the classification, as you're well aware, between the, instead of speaking about type of disease, it is level of disease 1 to 4, based on the location of the start of the chronic thromboembolic disease. Between the main pulmonary artery, lobar, segmental, and subsegmental ... with specimen that are similar to these, and a lot of the patients currently having surgery are Level 3 disease of the segmental level and occasionally subsegmental level as well.

This is just another view for a program in Toronto. The number of patients undergoing surgery typically is over 80% of the patients received will pass it with surgery after the evaluation [inaudible 00:03:39] and the CT pulmonary [inaudible 00:03:41]. Distal disease is not so much an exclusion criteria for surgery currently, it's more a combination of factors, comorbidities, occasionally patient refusal, but the vast majority of the patients are clearly surgical candidates.

But the high-risk patients are the patients who present with the high PVR greater than 1,200 Dynes and particularly in the face of decompensated right ventricular failure and even more so when you're looking at segmental and subsegmental disease and this is really the group of patients that carries ... greatest risk of surgery here. I'm certainly not experienced, and I'm sure in many centers...

So this is not a typical patient, so this is a patient, 55-year-old who had to have achondroplasia dwarfism. She presented with decompensated right ventricular failure, she was on face mask, 50%, and the BNP was over 2,000, bed-ridden, could barely get to the washroom. Mean PA pressure of 58 and cardiac index of 1.2 and a TPR of over 2,000, although we still, dwarfism, this is more difficult to assess accurately. But you can see on the CT scan the location of the disease in the distal segmental vessel, you can see the [inaudible 00:05:02] diffusion, distorted right ventricle and right atrium, so this is a patient who is anticoagulated present to you, we see death and, "How do you manage this patient?"

So, typically what we've been doing for this patient is to try to optimize them medically first, before considering surgery, so in-hospital with high dose IV diuretics. This is a group of patients where we feel there may be a benefit to start them on PH therapy pre-operatively, typically we do not treat anyone medically with PH therapy pre-op surgery, but that group of patients potentially to give a little bit more ... time to optimize them. We've been studying them on some PH therapy here, and we try to delay the surgery until we can optimize them as long they're progressing in the general condition. And over the past few years, this is a group of patients that we have also approached for pulmonary endarterectomy also with the discussion about the possibility of ECMO post-operatively as a breach to recovery in the face of decompensated right ventricular...

Now, post-operatively, this is where the difficulty comes. So there's [inaudible 00:06:14] optimization you can do in order to wean this patient from cardiopulmonary bypass, typically you wean them relatively slowly from the bypass, optimize their filling pressure, to optimize their right ventricular function without overloading the right ventricle, you optimize the gas exchange to avert any hypercapnia, optimize the oxygenation, you can optimize the heart rate with temporary pacemaker, and typically you can also use inhaled nitric oxide or potentially prostacyclin, and ... although we very rarely use milrinone, this is a group of patients who have benefit from some [inaudible 00:06:52] super ...

But the difficulties that once ... the RV decompensated ... becomes dysfunctional after the surgery that may lead to some degree of pulmonary edema, which raises the PH pressure, which increase the RV dysfunction. With RV dilatation, you will push on the LV, and then you get your vicious cycle with potentially more pulmonary edema, and it's really difficult to get out of that cycle without the use of ECMO, and ECMO will serve [inaudible 00:07:23], dramatically change the management of these patients, and you can potentially use it much more proactively in order to avoid the RV dysfunction and the pulmonary edema, and this is also to allow [inaudible 00:07:35] based on the long transplant experiences where a majority of patients no ... in some centers at least, will stay on the ECMO post-operatively until the RV has recovered to some degree.

So the ECMO really has been changing the practice over the past few years and these two pictures, this is two patients in Toronto in the year 2,000, when I was a fellow ... on the left-hand side, you can see how an ECMO patient would look like, a lot of machines, a lot of perfusion. You can see the dialysis machine on the bedside, patient is paralyzed and certainly not moving. And then, over the past few years, you have patients on ECMO who are doing treadmill at the bedside. This is a patient waiting for a long-term sponsor, really a dramatic shift in the management of these patients over the past few years.

This was related to the fact that now we have new oxygenators, which really have changed the field. We have also some centrifugal pumps, we have new cannulas, and we have heparin-coated tubing, so all these changes really have led what you are currently seeing with the use of ECMO, and the new oxygenators have really been ... probably the most important part in the change of practice.

These new oxygenators are made of PMP fibers, which are much more resistant and prevent any type of interface between the blood and the air, so the air doesn't damage the blood, the blood doesn't get inflammatory and ... these oxygenator with the PMP are much more resistant, so they can be used for several weeks, up to even three, four weeks without being changed and without creating any type of inflammatory or major inflammatory reaction within the blood. The other part that is beneficial is that the gas is circulating through the tubing, and the blood is outside of the tubing, so the resistance for the blood to circulate through the oxygenator is actually very low, so very minimal resistance to push the blood through the oxygenator, and it is the gas that's circulating into the tubing through this hollow fiber system.

So this was shown to reduce the red blood cell and platelet transfusion rate, much better gas exchange with oxygenator that were providing support for up to three, four weeks before it had to be changed, lower resistance, and also lower priming volume.

Now, the other change has the development of these Avalon cannula, which is a single cannula that can be advanced to the internal jugular vein with the tip of the cannula sitting in the IVC, the top part of the cannula sitting in the IVC of the ... and the blood is going into the patient, sorry, out of the patients to the pump, the oxygenator, and then comes back through another channel into the right atrium and then direct to the tricuspid valve into the right ventricle.

So the advantage of these cannulas, it is a single stage cannula from the upper part of the body, which allows mobilization. It has the limitation ... during placement, the tip has to be placed into the IVC, and so the best is to use the fluoroscopy machine in order to position it properly. If it goes into the right ventricle, there is a risk of right ventricular perforation. You have to position the cannula properly in order for the flow to be directed towards the tricuspid valve [inaudible 00:11:13], otherwise, if the cannula is not well-placed, it can affect the flow and that is still the main limitation of the cannula, is the placement. And if you have somebody who is quite corpulent, or large, it may not provide enough flow to oxygenate the blood adequately, in which case, you need to have two venous cannula, so one-one in different vein...

This is just one of our patients post-transplant, we can see that the cannula was advanced ... ended up in the right ventricle and was seen on the chest x-ray. Only, unfortunately, the right ventricle didn't perforate, but this is just to show the risk with this cannula once they get inside of the...

This is a patient post-pulmonary endarterectomy here. Patients who develop severe hypoxemia post-operatively, mostly from shunting [inaudible 00:12:01] and pulmonary edema, or at least a combination of both, but you can see that after a couple of days, the patient could be extubated, only spend about seven days on the Avalon cannula before it was removed and ... The Avalon cannula was placed basically over the [inaudible 00:12:17], so the [inaudible 00:12:18] was removed, the [inaudible 00:12:19] was advanced for the [inaudible 00:12:21], and then the vein was dilated, and the cannula advanced on to the IVC, so it is actually very easy to insert over the [inaudible 00:12:31], don't even need a puncture side, which makes it a lot easier ...

So what the options for veno-venous ECMO in CTEPH, mostly post-operatively, is for oxygenation issues, when you don't have much right ventricular dysfunction. If you have hemodynamic complications or difficulties, the ECMO will not provide hemodynamic support, and you will need to have central veno-arterial-ECMO or peripheral veno-arterial-ECMO for the femoral vessels, typically. Or you can use a PA-LA Novalung, which have been reported in a few numbers of cases.

Just a brief word on the PA-LA Novalung. Novalung is one of these new oxygenator PMP fibers, but the main difference with other oxygenators is that it has a very low resistance, and the blood can circulate at a rate of about 1.5 liter per minute with a gradient of only six millimeter of mercury. It has a very low shear stress, a smaller surface area than other oxygenator, and that's why it has a lower resistance as well, and you can have blood flow up to 4.5 liters or as low as .5 liters per minute, and the filling volume is only 250 mil, and it is heparin-coated.

So these cannulas can potentially be used as a parallel circuit with the long, so you can connect one cannula in the left atrium shown here. So this is a view of the patients from the left side through the [inaudible 00:14:09], the right [inaudible 00:14:09] vein, so you can put one cannula in the right [inaudible 00:14:13] vein that ends up in the left atrium, and the other cannula is placed in the pulmonary artery, so the blood is circulating from the pulmonary artery towards the oxygenator, and then it goes back to the left atrium through the [inaudible 00:14:26] cannula. You can see on the x-ray, the cannula that goes in the left atrium, the one that goes in the pulmonary artery ... and the advantage is that you don't have any pump; the right ventricle will generate the flow through the oxygenator.

So the patients post-operatively can be in bed extubated, and you have the cannulas that goes to the oxygenator and then the oxygenator blood going back to the left ventricle ... and the fact that you don't have any pump allows these patients to be a bit more mobile and also to potentially wait for longer until their transplant if it is a [inaudible 00:15:04] transplant.

And these are the patients who are waiting for transplants, so it is a good way to bridge patients to a transplant, particularly smaller-sized patients who may wait longer.

The flow through the PA-LA Novalung’ s about half, so about two to three liters, or two to two-and-a-half liters of blood will circulate through the PA-LA Novalung, and the other two to three liters will circulate through the pulmonary vasculature, and ... so there's a shift between the pulmonary circulation and the Novalung circulation that's shown in that case report from Germany here.

So this has been the experience for ECMO after pulmonary endarterectomy here ... the group in San Diego [inaudible 00:15:49] experience over ten years ago, mostly veno-venous type of ECMO, the group in Cambridge have used mostly central VA-ECMO ... in Vienna, peripheral VA-ECMO, as well as in Paris, peripheral VA-ECMO, and we have used central VA-ECMO predominately here. The indication has been variable, and you can see the rate varying between about 1% to 19% in Vienna, where the use of ECMO has been a bit more liberal, that's certainly the experience from the long-transplant program, I believe, where they use VA-ECMO as a bridge to recovery ... actively, easily in the PH of patients with [inaudible 00:16:29], but the other centers have had an ECMO run for about three to five percent, in general ...

This is the experience from Paris, where the decision for ECMO was made either inter-operatively or post-operatively based on the status of the patients. On inter-operatively, they've used PA-LA Novalung, central VA-ECMO, or peripheral VA-ECMO as a bridge to transplant most of them to recovery. And then, post-operatively they've had difficulty during the recovery phase, they've used mostly VA-ECMO as a bridge to recovery [inaudible 00:17:06] to transplant. They've had eight patients that have bridged to transplant with ECMO and four of them survived on the bridge to recovery with about 50% survival rate.

In our experience in Toronto, we have used the central VA-ECMO as a primary option, so when we have patients with severe RV dysfunction pre-operatively or [inaudible 00:17:31] RV dysfunction pre-operatively, we will discuss the possibility of ECMO and use it only if you have to as a bridge to recovery. So typically, we will try to wean off the patients from cardiopulmonary bypass with nitric oxide, optimization that I mentioned before, and occasionally [inaudible 00:17:48]. If that doesn't work, we will bridge them to the central VA-ECMO and by keeping them on VA-ECMO for two or three days. [inaudible 00:18:00] we allow the right ventricle to recover to allow the [inaudible 00:18:03] two or three days ... It is surprisingly good to see that the ventricle actually bounce back and very often that will allow us to wean off the VA-ECMO and to eventually close the chest and to continue with the progress.

If after two or three days, the RV has recovered, but the patients have remained some degree of gas exchange abnormality with some degree of pulmonary edema, we switch to VV-ECMO in order to wean the central VA-ECMO, close the chest, and then we use VV-ECMO if there is residual hypoxemia or hypercapnia. And if there's really no recovery of the right ventricle, this is a situation where we potentially will consider PA-LA Novalung as a bridge to transplant in the younger patients, but this is not something we have done, and again, we will select that as a very ... in a very small selected group of patients, but we will do that only after a few days of VA-ECMO to see exactly what happens to the PA pressure and the right ventricle.

So the principle that we use to manage central VA-ECMO ... We use the same site from cardiopulmonary bypass, so the same arctic site, which comes with [inaudible 00:19:18 necessary to do a normal cannula], which is a bit more easily to manage, and then we use one of the two venous site cannula, typically 28 French is enough to have adequate flow, and we do a very careful hemostasis before closing the skin, so the cannulas are inserted with a surgical field and then the skin is closed at one of them. And we do a very good hemostasis before closing ... can take a few hours sometime, but that really will help to manage the ECMO post-operatively if they are not bleeding.

And typically we will target a flow of about three liters with mean PA pressure of about 20 to 30, so the goal is unload the pulmonary vasculature, but not to displace all the blood, so you need to keep some degree of ejection to the right ventricle and to the lungs, the goal being to have some flow through the lungs so the pulmonary vascular system doesn't clutter. And also, if you want to ... resolve [inaudible 00:20:13] you need to have some degree of pulmonary perfusion for the pulmonary edema to resolve. We target an ACT of one-sixty to 200 or unfractionated heparin of .2 to .4, and typically we will target euvolemia ... it is quite difficult to dry these patients with [inaudible 00:20:31] as they are on VA-ECMO very often. If they start getting dryer, the venous sternum will start to chatter, and then rapidly you have to give feedback, and this is typically a time when you need to bring them off VA-ECMO.

So we bring them off with ... [inaudible 00:20:47] TEE, and then we increase the anticoagulation to wean, and then stop it for a few hours afterwards based on the bleeding situation. And once they're off VA-ECMO, then if necessary, we will switch them to VV-ECMO based on the oxygenation.

And this has been our experience with ten patients' bridge to recovery with ECMO. So seven of the ten patients we bridged, are on central VA-ECMO, and five of them after two to five days they're weaned from the VA-ECMO, two of them were weaned from VA and then started on VV-ECMO for another week afterwards. And you have two patients on VV-ECMO post-operatively and one on VV-ECMO, peripheral VA-ECMO post-operatively, and this is all the patients we lost on ECMO, the other patients were discharged from hospital.

So this is the patients I presented initially here. So we did the surgery here and then we kept her on VA-ECMO due to the RV dysfunction, and after two days we were able to wean off the VA-ECMO, [inaudible 00:21:51] intubated for seven days, and then discharged from the ICU at nine days. And then she rehabbed to some degree in the hospital because of her [inaudible 00:21:59].

And this is her at one year post-operatively. She reached to us last spring, and she was doing well, the BNP had no malaise, the RV function had no malaise and [inaudible 00:22:10], she had some residual elevated PA pressure and she was considered for medical therapy here. [Inaudible 00:22:18] be enough oxygen, otherwise...

The last point is that patients with decompensated right heart failure do often need more PH therapy in the longer term, so these are patients who need to be followed post-operatively, similarly to patients with high PVR pre-operatively ... and potentially don't normalize their PA pressure, but still have major clinical improvement.

So in conclusion, the distal segmental and subsegmental disease is accessible to pulmonary endarterectomy here. These level 3-4 diseases with high PVR, particularly in the face of decompensated RV failure have certainly high-risk category. On ECMO, maybe a good way to bridge them to recovery with good results. And in our experience, central VA-ECMO for two to five days post-operatively has been a good way to bridge them to recovery here.

And finally, I know that you all are members in the team in Toronto, with whom the program is running, and it is clearly a multi-person program and not a single person activity here.

Thank you for your attention.