Download David Jenkins’ slides here
Download Hiromi Matsubara’s slides here
Download Rishabh’s slides here
Transcript “SURGICAL INTERVENTIONS IN CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION”, APRIL 29, 2024
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DR ANDREAS REIMANN (MODERATOR)
Hello everybody, I’m Andreas Reimann, and I welcome you to this second webinar of the Alliance for Pulmonary Hypertension in 2024. I’m very happy that we can continue this series of webinars on progress in pulmonary hypertension treatment, driven by the recently published guidelines. Today, we are talking about the treatment of chronic thromboembolic pulmonary hypertension, a topic we discussed last year in November in a more general way. However, today we are focusing on interventions to treat this complication. I’m really honored to be joined by two esteemed speakers.
I welcome Professor Hiromi Matsubara from Okayama. Dr. Matsubara, I know it’s very early in the morning in Japan, and we are very pleased and honored that you made it at that time. We are also joined by Dr. David Jenkins from London, and Rishabh Radhakrishnan. Rishabh, I apologize for having difficulties pronouncing your name. You are a chronic thromboembolic pulmonary hypertension patient and you’re sharing your patient experience with us.
The Alliance for Pulmonary Hypertension is a non-profit organization that devotes resources to the advancement of the treatment of pulmonary hypertension and the empowerment of patients living and their caregivers.
Dr. Jenkins, if you are with us, welcome. You’re right on the spot. I’m moderating this webinar, and we are very honored that you and Dr. Matsubara are joining us this afternoon, this morning, or this night for this webinar. We will be starting with major surgery to treat chronic thromboembolic pulmonary hypertension. Dr. Jenkins, I suggest you start with your presentation. We’ll call up the slides for you.
DR DAVID JENKINS
Thank you very much for inviting me. I was asked to speak about pulmonary endarterectomy surgery for chronic thromboembolic pulmonary hypertension, and I am honored to be included in the webinar.
To set the scene, because I’m aware that not everyone in the webinar is a pulmonary hypertension physician, pulmonary hypertension—the new definition of pulmonary hypertension—is a mean pulmonary pressure of 20 mmHg and a resistance across the lungs of two Wood units. One of the difficulties of diagnosing pulmonary hypertension is that it’s not an easily accessible part of the body to measure the pressures, as you can see on the right-hand side. Pulmonary hypertension has to be measured with a catheter, an invasive procedure, unlike systemic blood pressure, which is easily measured by a cuff on the limb. This is one of the difficulties with this disease.
To briefly introduce chronic thromboembolic pulmonary hypertension, its caused by an obstruction in the pulmonary arterial circulation, resulting from an incomplete resolution of pulmonary embolism leading to pulmonary hypertension. In the majority of the patients the clots resolve naturally but in about 2 or 3 percent of patients that process doesn’t happen properly and we don’t understand why and the end up with pulmonary hypertension. Usually here is a delay of about 18 months in the diagnosis, and the difficulty is that the symptoms are not specific with exhaustion and breathlessness and fatigue and probably only three quarters of patients have a clear history of deep vein thrombosis or pulmonary embolism so that can be a distraction to physicians as well but it’s important to make this diagnosis because we know that in 2024 that there are 3 treatments available for these patients and chronic thromboembolic pulmonary hypertension is the most treatable form.
The treatments include pulmonary endarterectomy, which I will speak about, balloon pulmonary angioplasty, which Professor Matsubara will speak about, and some medical therapies as well for patients who aren’t suitable for either of the other treatments.
So this is what chronic thromboembolic pulmonary hypertension means to me and this is a montage of the specimens removed by pulmonary endarterectomy surgery showing all the cast of thrombus from the inside of the pulmonary artery in the lungs and this is why we think that this is a mechanical disease that can be either cleared by surgery or reducing volume by the balloons to improve blood flow to the lungs.
The above are the recommendations for treatment from the 6th World Symposium on pulmonary hypertension. The 7th World Symposium is going to take place this year at the end of June, beginning of July, in Barcelona. This treatment algorithm will be updated further with the most modern evidence, but this is the current treatment algorithm. It emphasizes the importance of making the diagnosis and then having a discussion with an expert chronic thromboembolic pulmonary hypertension team. The first decision is whether the patient may benefit from surgery or not, and if they do, pulmonary endarterectomy is the recommended treatment of choice. But if we don’t think they benefit from surgery, the next best treatment is the other mechanical therapy with balloon pulmonary angioplasty, which we’re going to hear about afterwards.
This approach is reflected in the newest clinical guidelines where all three treatments for chronic thromboembolic pulmonary hypertension get a 1B recommendation for therapy. The order of treatments should be as we saw in the algorithm, i.e. considering surgery first as that’s the main recommended therapy. If surgery is not suitable, then moving to balloon pulmonary angioplasty, and if there are no targets for balloon pulmonary angioplasty, to consider medical therapy.
Here is a cartoon showing the three treatments. Across the top you can see a pulmonary artery, the left pulmonary artery, and this cartoon emphasizes that surgery is better at treating the more proximal lesions, the bigger lesions within the pulmonary artery. Then when we get down to the smaller segmental and sub-segmental branches, the balloon angioplasty can work. There’s probably a bit of overlap with both mechanical treatments here, and then for the microcirculation, the drug therapies work. So, this is explaining really that those three treatments act at three different places within the pulmonary circulation, but there is a bit of overlap with the treatments.
This is just showing the imaging to diagnose chronic thromboembolic pulmonary hypertension and the importance of the imaging with the ventilation and perfusion scanners, the screening test, then an echocardiogram, and then accurate mapping of the pulmonary circulation so that the surgeon can decide whether there are targets for surgery and the angioplasty operator can decide whether there are targets for balloon therapy. These three important tests with a computer tomography pulmonary angiogram, a conventional pulmonary angiogram, and a magnetic resonance imaging pulmonary angiogram, can give the technicians the information they need to decide on which is the best treatment for each patient. Next slide.
Coming on to the pulmonary arteries and why we need to understand the anatomy and physiology of these arteries when we’re deciding on our treatments and when we’re carrying out those treatments. Certainly, for surgery, one of the difficulties is that the pulmonary arteries are deep within the middle of the chest. Ordinarily, they have up to five liters a minute of blood flowing through them, and the thickness of the vessel wall is narrow; it’s a thin-walled vessel, the pulmonary artery. Also, the lungs have a dual circulation so they get blood through the pulmonary artery but also a separate circulation from the bronchial arteries of systemic oxygenated blood from the aorta. For these reasons, the operation is quite an invasive procedure.
To divert most of the blood out of the pulmonary arteries, we go on the cardiopulmonary bypass circuit, the heart-lung circuit that’s used for most cardiac surgery. That diverts most of the blood away from the pulmonary arteries, but because of that bronchial co-circulation, the only way to remove all the blood from the pulmonary arteries is to completely arrest the patient and drain all the blood out of the body, and that’s what’s required to perform this surgery.
This image shows the heart-lung machine, which is used for pulmonary endarterectomy surgery. The main difference between pulmonary endarterectomy surgery and standard heart surgery is that both require the heart-lung machine, but for pulmonary endarterectomy, we also need to remove all the blood from the patient’s body to have a good view into the pulmonary arteries.
In order to do that safely, we need to cool the patient down because the brain is very sensitive to lack of blood supply. By cooling the patient’s core body temperature to 20 degrees Celsius, that gives us a safe time limit where we can drain all the blood out and preserve brain function. That means that we have about 20 minutes of safe time to do the dissection in the right pulmonary artery and the same in the left without any blood flow through the patient during that time. The procedure we use is called “deep hypothermic circulatory arrest”, which basically means we cool the body down and then we can safely drain all the blood out to give us a good view to do the operation. Next slide.
This is the surgical technique to do the operation. The principle is very simple: we clear the obstructions, and that reduces the pulmonary vascular resistance and the pulmonary artery pressure, allowing the right side of the heart to recover so that more blood can be pumped to the lungs. The patient gets improved exercise tolerance, less breathlessness, and in the future, a longer lifespan. The principle is very simple, but the procedure is technically relatively more complex. The approach is via median sternoctomy, so it’s an incision through the middle of the chest wall, as for any heart surgery, then on the heart-lung machine, cooling the patient’s body to 20 degrees, and the circulatory arrest. While that’s happening, we do an endarterectomy to remove the inner lining of the lung arteries to remove the obstructions.
This is a little cartoon showing what we do inside the pulmonary arteries.
At minute 14.23 of the webinar recording you will be able to see the video of a pulmonary endarterectomy surgery performed by Dr. Jenkins.
We open the left pulmonary artery and look inside. We raise an intimal flap on the inside of the pulmonary artery wall. You can see there is a thin wall, and we’re raising a plane on the inside of the artery and gently dissecting that plane around the circumference of the artery. You can see where it starts off; it’s very thin, and as it gets to the disease further down, it gets thicker. All the patient blood is drained out so we get a good view, and now removing some obstructions and some segmental branches, you can see this a thick fibrosed blood clot there called “little tails”, we dissect these out of the segmental branches and push the end of the remains of the vessel wall back as to remove the obstruction, as you can see they remove the whole specimen and show the inside.
These are our own outcomes from Royal Papworth Hospital looking at the series in around 2019 and looking at the patients over time. We can see that over time from cohort 1 to 4 outcomes have improved and there is a dramatic reduction in mean pulmonary pressure and pulmonary vascular resistance. You can see the mean pulmonary pressure halving after surgery, and the pulmonary vascular resistance reducing by almost two thirds. The risk of the surgery these days is relatively low and the mortality risk at 30 days is less than 2%: modern pulmonary endarterectomy practice has became similar to normal cardiac surgery.
There are many complications of this surgery, those of any surgery i.e. infection, bleeding etc. But there are some serious complications that are specific to pulmonary endarterectomy. These include airway hemorrhage, reperfusion lung injury, residual pulmonary hypertension or right heart failure. Occasionally there can be neurological injuries and strokes. The majority of those complications are managed by extra corporeal membrane oxygenation support and this probably halves the mortality risk of this surgery.
This slide shows that the trial we performed at Royal Papworth Hospital over ten years which shows that the cognitive function is preserved despite the circulatory arrest, and the brain function or the cognitive function is not declined.
The latest international registry data show the effect of mechanical therapies and drug therapy on patients with chronic thromboembolic pulmonary hypertension. You can see the survival after five years following surgery: the red line are the patients who had surgery, the green line are the patients who had balloon pulmonary angioplasty and the blue line are the patients who had drug therapy. You can see that the survival of the mechanical surgeries is around 90% while the patients who only had drug therapy without mechanical intervention was about 70% at 3-5 years following diagnosis, so this really emphasizes the importance of the intervention therapies.
This is our own data from Royal Papworth Hospital and it shows the activity, quality of life and symptoms from patients before and after pulmonary endarterectomy surgeries. Taking the CAMPHOR score, a low score means good i.e. the patient is happier with good quality of life and few symptoms and you also can see a significant reduction in all the scores in all the parameters following the surgery at one year after surgery. Most importantly this benefit is sustained up to 5 years.
So in conclusion, ladies and gentlemen and patients listening, the role of pulmonary endarterectomy is clear and it is the guideline recommended first line treatment in chronic thromboembolic pulmonary hypertension patients and still accounts for the majority of interventions.
The operation is reproducible with mortality of less than 2% in experienced units.
There is an immediate improvement in haemodynamics.
There are some specific complications but they can be treatable with extra corporeal membrane oxygenation and patients can benefit from its support.
The successful early outcomes translate into sustained improvement in quality of life and better long term survival.
The surgery can be part of a multimodality strategy for some patients who may require all three treatments but for the majority of patients it is the only treatment required.
and thank you all
ANDREAS REINMANN
Thank you very much for this fascinating presentation and for the absolutely fascinating figures you showed us and the improvement over time of that intervention.
Now, I am very honored to invite Professor Matsubara to talk about an additional way of treatment for some patients, which is called balloon pulmonary angioplasty. Professor Matsubara, if I’m not mistaken, you are really the pioneer of this minimally invasive intervention, and we are very honored that you are going to present insights about it.
PROF. HIROMI MATSUBARA
Thank you. These are my disclosures.
Dr Jenkins already talked about chronic thromboembolic pulmonary hypertension, but I would like to emphasize that this is a rare complication of acute pulmonary embolism. The stenosis or obstruction of the pulmonary artery in is caused by an organized thrombus. Organized thrombus is not merely a clot; it’s tissue-like, so anticoagulant or thrombolytic treatment is no longer effective to treat it. The go-to standard treatment for chronic thromboembolic pulmonary hypertension is to remove these tissues from inside the primary arteries by surgical procedure. Balloon pulmonary angioplasty is a treatment for chronic thromboembolic pulmonary hypertension. Patients diagnosed as inoperable had no mechanical treatment before the introduction of this intervention.
In the left side panel of this image, you can see the stenotic region at the area, and in the center panel, we are using the balloon dilation. The region could be dilated, and immediately after removal of the balloon catheter, you can see the region’s flow restored. So, it’s a very simple technique to treat only one or two regions, but chronic thromboembolic pulmonary hypertension usually sees many regions all over the pulmonary arteries, so we have to repeat it to almost all segmental arteries.
We have defined the balloon pulmonary angioplasty technique, but originally it was reported already in 1988, more than 30 years ago. At that time, it was only a case report.
The first case series was reported from the United States. Dr. Feinstein reported the results of bthe intervention in 18 cases. In this case series they performed an average of 2.6 procedures and six dilations for each patient. Mean pressure decreased from 43 to 33.7 mm mercury, but about 60% of patients developed complications after the procedure, including some severe ones, and one patient died. So, for inoperable cases, it appeared to be an attractive treatment option but, at that time, because of the too high complication rates and too low efficacy compared to pulmonary endarterectomy, this technique could not be spread to the rest of the world.
In Japan, because we didn’t have the experience, the surgical outcomes of balloon pulmonary angioplasty were very bad at that time. So, we decided to refine the technique in 2004 and reported our initial experience in 2012. At that time, 68 cases had already been treated with an average of four procedures. The diameter was almost double compared to the initial report, and we could decrease mean pressure from 45.4 to 24 mm mercury. However, 60% of patients developed severe complications after the procedure.
The decrease of the mean pressure was totally dependent on the number of treated segments, so it was natural that our results were much better compared to the initial report because we performed almost double the procedures and treated double the segmental arteries.
At the time we tried to dilate the region as large as possible, so we used a bigger balloon from the initial treatment. For example, in this case, we treated the right lower lobe artery and also the right upper lobe artery. After dilation, you can see proper and immediate venous return.
However, after the treatment, patients developed lung injury, as you can see in the front center panel. The patient’s lungs showed infiltration immediately after the procedure, and the patient needed to be intubated and required mechanical support to maintain saturation. In such cases, patients usually develop bloody sputum, and the computerised tomography images show bleeding around the dilated site, suggesting that aiming for complete dilation from the beginning of the region may cause primary injury due to hemorrhage from vascular injury. To prevent this, we have to use a smaller size balloon, especially in cases with high mean pressure.
The initial treatment just treats the stenotic regions of the unilateral side.
Then for the second procedure, we treat the opposite side of the lung with a bigger balloon and wait one month or two months. For the start procedure, we repeat the treatment and also treat the totally occluded regions with a big balloon to completely normalize the segmental arteries.
Finally, we treat the opposite side, so a stepwise dilation like this is necessary to achieve the final results.
For example, in this case, initially, the patient’s mean pulmonary pressure was 61 mm mercury. After one procedure the patient’s mean pressure decreased to 46. After the second procedure the patient’s mean pressure was about half of the baseline value. We waited one month and treated mainly the right side and, then we finalized the procedure by treating mainly the left side, with the patient’s mean pressure at less than 19. Only four rounds of balloon pulmonary angioplasty and no complications.
In this image. you can see that before the procedure,there are many stenosis or occlusions, and the distal flow is limited.
The lower panel shows the perfusion imaging. There are numerous defects, but after completing the four procedures, the patient’s pulmonary pressure became almost normal and perfusion also improved significantly.
Balloon pulmonary angioplasty is a minor interventional treatment but it is still invasive compared to medical treatment. I’d like to show what is the difference between medical treatment and balloon pulmonary angioplasty.
The case shown in the slide was in a randomized study comparing riociguat, a medical drug to treat chronic thromboembolic pulmonary hypertension, versus Balloon Pulmonary Angioplasty, and this patient was randomized to the Riociguat group. For one year, patients were treated with riociguat, and after one year, the pressure was almost the same as the baseline, and the perfusion, shown in the lower panel, showed a bit better perfusion, which could be seen by the green or yellow area. Mean pressure decreased about 5 mm Mercury, and 6 minutes walking distance increased, but the saturation remained almost the same.
After balloon pulmonary angioplasty, as you can see, the pulmonary angiogram became almost normal, and the perfusion was much better compared to one year after riociguat. The patient’s mean pulmonary pressure decreased and the most remarkable difference is the saturation. So not only the hemodynamics but also the saturation and oxygenation. After the treatment, patient symptoms were much better compared to receiving only medical treatment.
The multi center registry shows significant improvement of the functional class and hemodynamics, and decrease of mean pressure, immediately after balloon pulmonary angioplasty. This was maintained at follow-up, and at that time patient three-year survival rate was about 90%.
In 2012 only two countries, Japan and Norway, were performing balloon pulmonary angioplasty as a treatment for chronic thromboembolic pulmonary hypertension, but 10 years later, many countries are following our success, and now it has become a treatment option. Current guidelines recommend balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension cases.
This slide shows the global outcomes based on the multi center registry and the prospective randomized study. Our results show that the mean pulmonary pressure decreased about 40-50%, and pulmonary vascular resistance about 65%. However, the European registry performed in Poland showed that the mean pulmonary pressure decrease was about 30%, so it was probably due to the difference in experience. Indeed, after experiencing many cases, current prospective randomized studies from Japan and from France showe almost the same results: mean pulmonary pressure decreased about 40% and pulmonary vascular resistance decreased about 60%. Please note that the 30-day mortality previously in Japan was 2.6% and in Poland 1.7%, but in the randomized study in France, it was 0%, and in Japan also no one died.
So as a summary, balloon pulmonary angioplasty was born in 1988 and grew up in Japan, so we just refined the technique and the safety and efficacy. Balloon pulmonary angioplasty have been established and is accepted globally as a treatment option for inoperable chronic thromboembolic pulmonary hypertension. Thank you for your attention.
ANDREAS REIMANN
Thank you very much, Dr. Matsubara, for this enlightening presentation. You showed us that there is a dramatic improvement in the outcomes, and we’re very happy that we could witness such excellent results. Now, Krishna is a patient who underwent balloon pulmonary angioplasty. Rishabh, you want to share with us your experience. Please go ahead.
RISHABH
Hello everyone, my name is Rishabh.
I’m a student at the National University of Singapore. I was diagnosed with Chronic Thromboembolic Pulmonary Hypertension in September of 2022, and over the next 15 minutes, I’d like to share with you a journey that my family and I have been through from diagnosis to cure. But just before that, I want to thank Professor Matsubara and Professor Jenkins for all that they’ve done over the past few years to help thousands of chronic thromboembolic pulmonary hypertension patients like myself.
My journey started around July 2022 when I had just completed my 2-year army service after high school. That’s a picture of me with my grandparents before diagnosis. In Singapore, all men are required to serve in the army after school, and this was by no means an easy experience, but overall, it was extremely positive for me. I had just started university in August immediately after the army, and around that time, symptoms started to develop, primarily in the form of exertion intolerance. I was very passionate about running during my days in the army; I would frequently run 10 kms with ease, and in July 2022, I noticed a steep drop in my stamina, which didn’t make any sense to me or my family. What really frightened us was a loss of consciousness one time as I was crossing a road, but fortunately, I was with my friends who helped me. This prompted my parents and I to seek the help of a pulmonologist, and he initially diagnosed me with asthma and started me on a spray, but this treatment didn’t show any improvements.
I underwent more testing, and later blood tests and computer tomography tests confirmed the possibility of pulmonary embolism, which we understood was easy to address, although still very concerning. Unfortunately, however, when the right heart catheterization and pulmonary angiogram procedures were performed, my doctors at the time confirmed chronic thromboembolic pulmonary hypertension. As part of the procedures, various hemodynamic measurements were also taken. While mean pulmonary arterial pressures, or MPAP, under 20 is considered normal, we learned from the right heart catheter that mine was around 36, which confirmed pulmonary hypertension. The measurement of cardiac output seemed normal at the time, which is the amount of blood that the heart pumps out in a minute, but this is later established to be incorrect and probably lower. I was started on anticoagulants and three months of observation as per the standard protocol for chronic thromboembolic pulmonaryhypertension. This picture was taken when I was hospitalized during diagnosis in September 2022.
So the next two months proved to be very challenging for me because I tried to lead as normal a life as possible, and I refused to postpone university as well while my symptoms continued to worsen. So this is a picture of me with the FIFA World Cup chart, keeping track of the matches. I’m hugely passionate about football, and I couldn’t play anymore as I would be breathless after walking merely half a kilometer, but I could still watch and enjoy football. The second picture was taken in October 2022, so I was at a restaurant again, trying my best to retain the life of a normal university student, and you can see how skinny I’d become as a result of the disease.
I was around 62 kilos during my time in the army, and in that picture, I believe I was 55. Just for context, I’m 177 cm tall, so periodic echocardiogram tests continue to show no signs of improvement to measurements such as the size and shape of my right ventricle, pulmonary pressures, and my stroke volume, which is the amount of blood that the heart pumps for every beat. I was a very fit person before chronic thromboembolic pulmonary hypertension as well, and now my resting heart rate was typically around 90 beats per minute because my heart had to work a lot harder to get the body the oxygen that it needed. So my parents and I spent a lot of time understanding my treatment options and the possibility of either a pulmonary endarterectomy surgery or the balloon pulmonary angioplasty procedures. In fact, at the time, we had reached out to Royal Papworth Hospital and discussed my case with one of Professor Jenkins’s colleagues, and the assessment was that I was a good candidate for Pulmonary Endarterectomy, but we started to consider the balloon pulmonary angioplasty as our preferred option.
Towards the end of November, just over two months since diagnosis, I experienced a sudden deterioration of symptoms. I would get out of breath walking barely 50 meters at a very slow pace. I had a couple more instances of losing consciousness when exerting even tying my shoelaces would make me feel lightheaded, and I also developed a new symptom characterized by hoarseness of the throat, which is known as Ortner’s syndrome, and that’s considered very rare in chronic thromboembolic pulmonary hypertension patients. It’s caused due to the compression of my left laryngeal nerve, and as a result, my voice became very hoarse. I could only talk softly; it felt as if I had a permanent sore throat.
Due to this sudden deterioration of symptoms, our doctors in Singapore and I agreed on the acceleration of next steps, and we made the decision to go ahead with balloon pulmonary angioplasty. Our decision on treatment options was driven by two factors. Firstly, pulmonary endarterectomy is a major heart surgery, and, as Professor Jenkins explained, it has a long recovery process. The balloon pulmonary angioplasty, on the other hand, consists of multiple interventional procedures requiring just an overnight hospital stay and immediate recovery. And secondly, my parents and I felt that published data showed comparable results between the pulmonary endarterectomy and balloon pulmonary angioplasty, but it’s very important for me to emphasize that this is just our personal opinion and preference based on what we had read at the time.
This is a picture of me after my first balloon pulmonary angioplasty, when I regained consciousness from the sedation. At that point, my parents and I were extremely hopeful that my recovery would now commence. We had no idea at the time how bad the next couple of months were going to be, so subsequently, four more procedures were performed between November and January, in Singapore, and there were brief moments during these months that I experienced small improvements, but the symptoms would always deteriorate again. So through all four procedures, my mean pulmonary pressure was measured at between 45 and 50, and stroke volume measurements through echocardiograms also showed no improvements, and my resting heart rate continued to be around 90, and it would shoot up upon light exertion such as walking.
At the end of my fourth Singapore balloon pulmonary angioplasty, we took some more hemodynamic measurements, and they looked very bleak. My mean pulmonary pressure was 44, and I had very low readings for cardiac output as well, and at that point, the prognosis didn’t look too great. So my doctors back then advised possible microvascular disease as a reason for no improvement, which is when chronic thromboembolic pulmonary hypertension impacts very small blood vessels that even a balloon pulmonary angioplasty can’t address. So, at this point, the options were to extend life by a few years through medication, or the very extreme option of a lung transplant, and my parents, who I am, of course, so thankful to, have conducted extensive research since my diagnosis. Naturally, they were extremely worried, and they did everything they could to try and find a solution. My father, in particular, spent sleepless nights reading research paper after research paper. Towards the end of January, my father reached out to the Okayama Medical Center, requesting an urgent video consultation with Professor Matsubara. So we had known about Professor Matsubara as well as Professor Jenkins and their expertise in chronic thromboembolic pulmonary hypertension almost since diagnosis, but it was only now that we had finally contacted Professor Matsubara, and we felt the balloon pulmonary angioplasty procedures were the best solution for us, and he was very kind to give us time for an urgent consultation as my condition was quite grave. We requested him to take me as a patient and consider me for his balloon pulmonary angioplasty treatment, and based on his evaluation of my reports and scans, he felt confident that he could restore me to at least near normalcy. At that point, my parents and I felt elated; it felt like we had been drowning and Professor Matsubara had given us life jackets.
Within weeks we were on a flight to Okayama for treatment in February of 2023. So this is a picture of me on my flight to Okayama in February. It’s a bit difficult to see, but I’ve got oxygen going into my nose via a cannula, and that’s a professor Matsubara’s recommendation as a precaution for high altitudes. So the last couple of weeks before our trip to Okayama in February, they seemed like there seemed to be minor improvements of symptoms, and we even wondered if the Singapore balloon pulmonary angioplasty had started to gradually work, but from the day of travel to the next day when I was admitted at the hospital, symptoms deteriorated rapidly again. Each time I experienced some improvements, it was like pushing a ball up a slope. If you let it go before getting to the top, it would start rolling down again. So I remember the next morning, sorry, the morning I was about to get admitted into the hospital and nearly lost consciousness while tying my shoelaces in the hotel.
I was admitted to Okayama Medical Center for four days during which Professor Matsubara’s wonderful team performed two balloon pulmonary angioplasty procedures, and the hemodynamic measurements at the end of those two procedures were dramatic. We immediately saw a 30% drop in mean pulmonary arterial pressure and a huge jump with complete normalization of stroke volume and cardiac output. Until discharge, of course, I couldn’t really test how I felt after the procedures when exerting, even though measurements were unbelievable to my family and I, but right from the point I stepped out of the hospital, I noticed an incredible improvement in my symptoms. I actually didn’t feel anything with normal exertions such as brisk walking and gentle slopes. This picture of me is in Osaka just one day after discharge, and I remember my dad and I going for a long walk at a brisk pace, and it was incredible. I felt completely normal. Normally, we take for granted the amazing system our body has, from the point we take a breath to the point where the oxygen is delivered to our muscles, organs, and cells, but here I was actually experiencing the significance of this incredible process. So after returning to Singapore, we tried out stairs, and my parents were naturally extremely nervous, but I felt absolutely nothing. I was completely fine, completely normal. My resting heart rate had also normalized, and it dropped to a healthy 60 beats per minute. So I could do normal life stuff at this point, normal life stuff that a typical young person would do, such as climb stairs two steps at a time, sprint to catch the bus at university, walk to my classes. The only constraint was that I’d been advised to not commence exercise as my treatment was not yet completed.
We returned to Japan in May as planned for additional balloon pulmonary angioplasty procedures, and I’ve been feeling amazing since my February procedures. After so many stressful months, my parents and I also had a holiday in Tokyo and Kawaguchiko near Mount Fuji, and as Kawaguchiko is at an 800-meter altitude, my parents were worried if I would feel any discomfort since there’s reduced oxygen saturation at high altitudes, but thankfully, I was completely fine, and we had a wonderful holiday there. Then we headed back to Okayama for my final treatments, and the measurements taken before the start of the procedures showed complete normalization of my pulmonary pressures. Professor Matsubara, in some of his papers, describes this as the spontaneous enlargement of pulmonary arteries after balloon pulmonary angioplasty. I could literally see it in the measurements and feel it through symptoms that had completely vanished. My mean pulmonary pressure had dropped from 45 to 50 during diagnosis to 33 in February and 19 in May. So at this point, my pulmonary pressure, as well as cardiac output, were both already within normal levels while at rest, and after three additional procedures in May, my mean pressure further dropped to 16 as we returned to Singapore, with my right ventricle shrinking to normal size. The hoarseness of my voice also fully normalized, and thankfully, there had been no permanent damage to the laryngeal nerve.
So how am I doing now? Well, you can see me playing university football, which is perhaps what I missed most when I had chronic thromboembolic pulmonary hypertension. I now work out, study, I had an internship in December, and I have another one lined up over the summer, and of course, I enjoy hanging out with my friends, going on holiday with my family. Additionally, the only medication that I continue to be on is anticoagulation, warfarin to be specific. I also underwent physio with a heart and lung physiotherapist in Singapore, and my physiotherapist, Jaclyn, was extremely helpful in getting me back into running. These pictures are essentially moments of me leading my normal life after four balloon pulmonary angioplasty procedures in Singapore that had failed and then five in Japan that saved me.
There is a picture of my parents and I with Professor Matsubara at dinner when he visited Singapore. He particularly enjoys chili crab in Singapore, which is what Singapore’s famous for. Since Professor Matsubara is on his webinar, I just wanted to say my family and I will forever be grateful to you, not just for saving my life but giving me back a normal life. As a young person, I wanted to conclude by telling all chronic thromboembolic pulmonary hypertension patients who are watching this webinar to not lose hope. It is, of course, a horrible condition that robs you of the smallest pleasures in life, such as going for a walk or visiting restaurants with your friends, and also has a deep mental impact on not just the patient but also the family. But there is hope as long as you find the right doctor to treat you. There are solutions such as balloon pulmonary angioplasty or pulmonary endarterectomy to significantly improve the quality of life and even be completely normalized like me. Lastly, I wanted to express my gratitude to the Alliance for Pulmonary Hypertension for inviting me to share my experiences over this webinar. Thank you so much.
ANDREAS REIMANN
Thank you so much, Rishabh, for sharing your story with us, and this is really impressive, really adds from a patient perspective. Thank you, Dr. Jenkins and Dr. Matsubara, for sharing with us. We have a few minutes left for questions, and actually, Rishabh, you mentioned that you had four interventions in Singapore without success, you had five in Okayama with success, and we actually do have a question by Louise Bouman, she’s asking, “After how many balloon pulmonary angioplasty procedures, on average do people feel the difference in quality of life?”
DR MATSUBARA
Okay, thank you for your question. Usually, the initial procedure, initial one or two procedures show the greatest effect on quality of life, and, as Rishab said, usually, after discharge from the initial admission, patients already performed the two procedures, and after that, almost all patients realize that their shortness of breath disappears and could do everything as before.
ANDREAS REIMANN
Okay, thanks very much. We have another question by Louise Boumann “Although you mentioned no cognitive effect of this procedure, I hear a lot of people suffering with concentration problems for a long time after the procedure. Do you know any numbers of the issue?” I think this question goes to both. So if you, Dr. Jenkins, if you could start, and then Dr. Matsubabra.
DR JENKINS
Yes, thank you, temporarily after any major operation with a general anesthetic, if patients are on narcotics, they can have difficulties with concentration early on after major surgery, but we did the definitive, randomized trial of pulmonary endarterectomy and cognitive function back in 2011 which was published in the Lancet journal, and we looked at blinded, very detailed, cognitive assessments, and pre-surgery, at three months after surgery, and one year after surgery. Across all the groups, patients were better at one year after surgery compared with what they were before surgery. Cognitive function improved, and to do the complex cognitive function tests, they had to have good ability to concentrate, so we think it’s related to improvements in hemodynamics and oxygenation, so patients by one year had better oxygenation and better blood flow to the brain, and their cognitive function was actually better following surgery than before surgery, so in our practice, with our protocols, we don’t really see patients with impairment of concentration, especially in the longer term. It doesn’t seem to be an issue. Thank you.
DR MATSUBARA
So from the beginning, because, we have no previous data, before routinely performed the right heart catheter every year until five years,and after that, repeat at 10 year after the treatment, and, based on our experience, not yet published, but our experience shows that once improve hemodynamics could be maintained at 5 years and probably at 10 years, because 10 years, not all patient performed right heart catheter, but five years almost all cases performed right heart catheter and confirm that no deterioration observed, and regarding the functional class or six minutes walking distance 15 years, after the procedure show a bit of deterioration, the short became shorter, but probably because of age, because, at the treatment patient age average 60, currently 65 years old, and 15 years meaning that 80 years old, the six minutes walking distance, of course, shortened, but, daily life maintained, and if the patient sufficiently treated with anticoagulation, even after the treatment, no recurrence, or no deterioration could be observed, so the most important thing is to achieve the best result immediately after the procedures.
ANDREAS REMIANN
With a question from myself, there is a question from the Singapore pulmonary hypertension association, from Melissa Chan: “Amazing work, question for Dr. Matsubara or Dr. Jenkins, any hypothesis on why the balloon pulmonary angioplasty procedures in Singapore were unsuccessful? and may I add my question, how easy it is for patients to find the right centers doing pulmonary endarterectomy or balloon pulmonary angioplasty in the world. I mean, not every patient, of course, is lucky to go to your centers, so how easy is it to find the right centers?”
DR JENKINS
Yes, that’s a difficult question, really, and it’s about access to treatments. Ideally all patients should have the best treatment in the most experienced centers, but, sadly, that’s not always possible. We give opinions on lots of patients from around the world about having surgery, some do travel to to Papworth Hospital in Cambridge to have their operations, and we’re happy to do that, but unfortunately, it’s only those with financial resources can do that. In the United Kingdom we have a National Health Service, and all our own population have access to treatment for for free, but for international patients, that isn’t available, so we are happy to offer surgery to any patients around the world, and we give opinions on many patients, for free, but if they come for surgery, the hospital has to charge for that and it’s expensive surgery. We’re not a charity and that means that some people sadly don’t have the resources to travel to the United Kingdom to have surgery. We’re trying, with myself and colleagues, and lots of the experienced chronic thromboembolic pulmonary hypertension operators around the world, to educate and help starting centers, I have been twice to Singapore and operated on patients in Singapore on two occasions to to help the team there learn to do balloon pulmonary angioplasty and pulmonary endarterectomy.
I’ve been to lots of places all around the world, I was in Sydney last month helping the surgeons there with this operation, so we do our best, but, it’s about trying to educate doctors as much as we can. The difficulty is that these procedures are technically quite demanding and experience counts, and the best results are obtained with the people who’ve been doing it for 20 years or so and are doing multiple procedures every week, and there’s no easy answer to that, I’m afraid.
ANDREAS REIMANN
Also the question why didn’t it work in Singapore, why work in Okayama, I appreciate that may be a very hard question to answer.
DR JENKINS
I think I probably answered that well for him to spare his blushes,the team is a much more experienced balloon pulmonary angioplasty operator than the team is probably in Singapore.
DR MATSUBARA
Probably one thing only one thing I can say is, if you decide to receive balloon pulmonary angioplasty in your country, please ask the doctors how many cases they have treated until now, so for us, the initial 100 cases are necessary to develop the technique, but nowadays, we already published our experience, and probably, not so many cases are necessary, but at least I think 100 procedures, it’s meaning that at least 25 cases, experience would be necessary to complete the balloon pulmonary angioplasty.
ANDREAS REIMANN
RIght, thank you very much for your insights, for your time, at this early morning hour Dr. Matsubara, and we really appreciate your time, unfortunately, we are already over time, but I think it was quite certainly worthwhile.
I would like to invite the audience to watch out for our third webinar this year on May 28th, and this will be about congenital heart disease and pulmonary hypertension with Professor Maurice Beghetti as a speaker, and with that, I’d like to thank you all for listening and for presenting and wish you a very nice rest of the day, thank you, bye.