HOW COULD PiCSO® INTERVENTIONAL TRANS-CORONARY SINUS TECHNOLOGY REDUCE HEART FAILURE POST-STEMI?
On the 30th of October 2020, Miracor Medical SA sponsored a GISE webinar and were honored to invite a renowned international faculty of: Prof. Giampaolo Nicolli, Dr. Azeem Latib, Dr. Gianluigi De Maria, Prof. Adrian Banning and Prof. Antonio Colombo. The title of the webinar was ‘The role of the Pressure-controlled Intermittent Coronary Sinus Occlusion (PiCSO) interventional trans-coronary sinus technology to reduce heart failure post-STEMI’. This article summarizes the key discussion points of the presentations. If you wish to have a deeper overview we warmly invite you to watch the video of the recorded webinar.
Prof. GIAMPAOLO NICCOLI
Professor of Cardiology at the Catholic University of the Sacred Heart, Rome
Professor Giampaolo Niccoli introduced the webinar and moderated the Q&A.
Before introducing the first speaker, Prof. Niccoli reiterates that re-hospitalizations for heart failure after myocardial infarction are quite common, affecting almost one-third of patients3. Beyond the medical and quality of life implications, this is an important economic complication as the burden for the healthcare system is significant.
With the PiCSO interventional trans-coronary sinus technology we aim to reduce infarct size which, potentially, could lead to a reduction in de novo heart failure post ST-Elevation Myocardial Infarction (STEMI).
Dr. AZEEM LATIB
Director of Interventional Cardiology and Structural Heart Interventions at Montefiore Health System, New York
“This symposium is on a very interesting technology that, I think, addresses an unmet need. It has the potential to be an important part of what we do for primary PCI.”
During the e-webinar, Doctor Azeem Latib discussed the literature related to the clinical outcome of primary PCI in STEMI and the incidence of progression to heart failure.
Over the past fifty years, a number of medical advances have led to a significant reduction in cardiovascular mortality and other complications. However, cardiovascular diseases remain the leading cause of mortality worldwide, with more than seventeen million deaths globally1. According to the GRACE Registry2 and the SwedeHeart Registry3, STEMI accounts for approximately one-third of acute coronary syndrome hospital admissions. However, despite procedural and pharmacological iterations, mortality associated with primary PCI seems to have reached a plateau over the last decade3.
The CALIBER study4 examined data on approximately 25,000 patients and observed a 23.6% incidence rate of de novo heart failure after myocardial infarction. Some of the risk factors can be socioeconomic, age and diabetes. But, according to Dr. Latib, the most important predictors for poor clinical outcomes are the resulting infarct size and the incidence of microvascular occlusion. This has been confirmed in a pooled metaanalysis by de Waha et al. in 20175, showing infarct size and, even more, microvascular obstruction as independent predictors for heart failure rehospitalization post STEMI and mortality.
A more recent paper in 2020 by Xie et al6 demonstrated that even if TIMI-3 flow is achieved during the primary PCI, up to 42% of patients exhibit signs of delayed microvascular perfusion and an additional 40% of patients have microvascular obstruction. Therefore, Dr Latib reiterated that ‘we need to start concentrating on the microcirculation and what we can do to increase myocardial perfusion at a microcirculatory level’. In his concluding comments, Dr. Latib observed that the PiCSO technology ‘can be part of the solution as it has the potential to decrease infarct size and to improve microvascular perfusion’.
Dr. GIANLUIGI DE MARIA
Interventional Cardiologist – Consultant Cardiologist
at Oxford University Hospitals, Oxford
“The Pressure-controlled Intermittent Coronary Sinus Occlusion therapy use a coronary balloon placed in the coronary sinus to achieve flow redistribution.”
Doctor Gianluigi De Maria discussed the history and science of the trans-coronary interventional techniques.
The cardiac venous anatomy is comprised of three interconnected venous systems: (i) the coronary sinus system, (ii) the anterior cardiac vein system and (iii) the thebesian vein system. They are connected to only one arterial system, and their microvascular area is six times larger than the arterial microvascular area. This remarkable convergence means that it is possible to safely achieve bloodflow redistribution by increasing pressure on one end of the venous system; this is exactly what a trans-coronary sinus intervention does. However, to minimise risk of haemorrhage or other complications, animal and human studies7 have shown that this increase must be controlled and intermittent. Uniquely, PiCSO therapy requires the use of a console running the proprietary Wien algorithm, which constantly measures the patients’ coronary sinus pressure during the cardiac cycle to adjust the intermittent balloon inflation and deflation time to prevent venous damage during delivery of the therapy. During the balloon inflation phase, the arterial blood is redistributed to the infarct area at risk thanks to the activation and recruitment of collaterals. At the same time, the increasing density of the blood creates a plasma skimming phenomenon upon balloon deflation. Also during this deflation phase, the dramatic reduction in coronary sinus pressure creates a ‘suction-like’ effect, which facilitates the washout of the microdebris and deleterious agents associated with the infarct8.
The results of these phenomenons are brilliantly showed in a case report by Dr. De Maria, through the measurement of the index of microcirculatory resistance in a STEMI patient undergoing primary PCI and PiCSO therapy.
Prof. ADRIAN BANNING
Consultant in interventional and general cardiology
John Radcliffe University Hospital, Oxford, UK
President of the British Cardiac Intervention Society
“PiCSO is a novel and exciting therapy that can improve outcomes for our patients, and it may have a significant role for those patients particularly at highest risk.”
Professor Adrian Banning addressed the current PiCSO evidence and the future pipeline in STEMI clinical research.
The PiCSO Impulse System holds a CE-mark for use in patients older than eighteen years old evidencing anterior STEMI, presenting within twelve hours after onset symptoms and with TIMI flow 0 or 1, in whom primary PCI is amenable. Typically, these are the patients having the higher risk for large infarcts. The multi-center PiCSO in ACS study9 compared 22 PiCSO patients (with TIMI flow 0-3) to 58 ‘propensity score matched’ controls. The study demonstrated that PiCSO is associated with a 33% relative reduction in infarct size when compared to the control group, measured using Cardiac Magnetic Resonance Imaging (C-MRI). In a secondary sub-group analysis, patients with anterior STEMI with TIMI flow 0-1 had a more pronounced reduction in infarct size with a relative reduction of 49% after PiCSO therapy.
The single center OxAMI-PiCSO study10 has also shown promising results. It examined outcomes in STEMI patients exhibiting signs of microvascular impairment diagnosed using an Index of Microcirculatory Resistance (IMR) score >40 units. In this study, patients were assessed immediately poststenting and 24-48 hours later. The key finding was that there was a statistically significant reduction in IMR associated with the use of PiCSO. Indeed, 90% of PiCSO patients saw their IMR return to a ‘normal’ figure of 25 or less, whilst only one-third of control patients experienced the same. This study also required C-MRI measurement at six-months post procedure and PiCSO was associated with a significant 30% relative reduction in infarct size.
Miracor Medical is now building a robust clinical program, so we can identify which patients will benefit from this technology. Over the next four years, we will recruit more than seven hundred patients in 3 randomized clinical trials in Europe and the USA to get data on clinical outcomes per patient subgroup so that physicians can adapt the therapy to the different targeted applications.
Prof. ANTONIO COLOMBO
Interventional cardiology & Cardiothoracic surgery specialist
Director of Cardiovascular Interventions in San Raffaele Scientific Institute, Milan
Visiting Professor of Medicine at Columbia Medical Center, New York
"It is very difficult to make a statement from a single case, but when you see something so unique your mind starts making funny considerations and dreams."
Finally, Professor Antonio Colombo discussed the possible directions for future scientific research in other indications.
In a provocative final session, Dr. Colombo discussed the possibility of future studies to demonstrate potential PiCSO safety and effectiveness in off-label indications. He discussed its potential cardio-protective role in high-risk PCI, for patients presenting with significant Left Main diffuse disease undergoing rotational atherectomy with rotablator. He stated that ‘PiCSO therapy makes a lot of sense in this case to improve perfusion in
a procedure, which congests the distal bed and would have unique advantages against balloon pump’. The action of PiCSO on the microcirculation during procedures leading to distal compromise is interesting and would have to be explored with a robust clinical study.
The second indication was demonstrated by presenting a case study of compassionate use11, where PiCSO therapy was used on a patient with severe acute left ventricular dysfunction who was not recovering despite extracorporeal membrane oxygenation. Repeated coronary angiography due to persistent severe left ventricular dysfunction after fifteen days showed no changes, and PiCSO was performed on the 17th post operation
day. Twelve hours after the therapy, the echography showed recovery of the left ventricular function. This anecdotal isolated case report raises the possibility of proving PiCSO feasibility in off-label indications.
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