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The immediate and long-term prognosis of patients experiencing an ST segment elevation myocardial infarction (STEMI) has changed dramatically since the introduction of coronary reperfusion therapies during primary percutaneous coronary intervention (pPCI). The evolution of these therapies accelerated with the understanding that STEMI is caused by occlusive thrombus compromising flow in an epicardial coronary artery^1,2. Initially, drug-based dissolution of the occlusive thrombus was the only therapeutic modality, but this has been superseded by mechanical recanalization and breakdown with wires and balloons with improved outcomes^3,4. The intervention in STEMI is completed with stent implantation and dual antiplatelet therapy that secures the patency of the relevant culprit epicardial coronary artery. A significant body of evidence demonstrates that this reperfusion strategy has dramatically changed the outcome of STEMI and reduced in-hospital mortality to a single digit percentage rate^5-7. Generally, the earlier a patient with STEMI arrives in the catheterization laboratory, the better the outcome^8,9. Out-of-hospital emergency services and hospitals have been reorganized to shorten the time from first contact with a patient with STEMI to the time that the coronary artery is opened, and myocardial reperfusion is secured^8-10. However, while in-hospital mortality following STEMI has been reduced by the advances in pPCI, the number of hospitalizations for heart failure following acute myocardial infarction is still high over the past decades and is associated with poor prognosis^11-12.

The area at risk (AAR) is the region of the myocardial bed supplied by the infarct related artery (IRA). In the era of reperfusion, not all the AAR will become infarcted. Depending on time to reperfusion from onset of symptoms and the exact location of occlusion, there will be a proportion of the AAR (jeopardized but not infarcted) that can be salvaged by reperfusion therapy. This can be calculated as AAR−infarct size^13(figure2).

The fundamental basis of treatment of STEMI is driven by the paradigm that myocardial necrosis is irreversible. Accordingly, the higher the loss of functional myocardium, the larger the infarct size and the higher the chances for poor patient outcomes. A second important concept is that during STEMI, several degrees of myocardial damage occur, ranging from necrosis, which is irreversible, to injury, which may be reversible. Thus, reperfusion therapy is directed to minimize necrosis and reverse myocardial injury. Significant necrosis and loss of myocardial infarction is associated with high rates of in-hospital morbidity and mortality, and poor long-term prognosis^13-16.

The most worrisome syndrome that develops in patients with STEMI and large myocardial loss is heart failure: Necrotic myocardium is replaced by fibrotic tissue, and remodeling of the left ventricle is the mechanism that compensates for myocardial loss¹⁷. Strength and mass of the fibrotic tissue are extremely critical in the remodeling process. Regeneration of the necrotic myocardium after myocardial infarction is probably minimal, if occurring at all. Replacement of the fibrotic scar with viable myocardium is the holy grail of regenerative medicine, but as of 2021 has not reached clinical medicine. It can be estimated that up to 30% of patients presenting with acute myocardial infarction (AMI) develop heart failure within 1 year following PCI with even more patients among those presenting with STEMI^11,12.

As “time is muscle” for re-establishing coronary flow in patients with STEMI, two measurements of standard-of-care were developed: (a) time to first medical care, and (b) door-to-balloon time. The shorter the time from onset of symptoms to intervention and re-establishment of coronary flow, the better the outcome for the patient⁸. Multiple studies have shown that patients with extensive myocardial loss are at higher risk to develop short- and long-term complications of acute myocardial infarction. The in-hospital course of patients with significant myocardial loss is characterized by mechanical and electrical complications such as heart failure, atrial fibrillation, ventricular arrhythmias, pericarditis and left ventricular thrombus. Long-term outcomes are typically dominated by heart failure, and ventricular and atrial arrhythmias, both of which result in poor quality of health and high use of long-term medical resources^8-10.

The current standards of care that are recommended by professional guidelines are implemented and regulated in many countries. These include 90-minutes from entry to the hospital to culprit lesion crossing. However, most recent guidelines recommend reducing this time to 45 minutes which requires an operative catheterization laboratory 24 hours every day all year round¹⁸. Out-of-hospital emergency services are required to perform electrocardiograms as early as possible, to inform the hospital immediately when STEMI is diagnosed, and to transfer patients directly to the catheterization laboratory after loading anti-platelet aggregation drugs and heparin^19-21.

Risk factors for extensive myocardial loss include late arrival for therapy (>6 hours from onset of pain); complete occlusion (TIMI flow 0-1) on arrival of an artery that supplies a large myocardial territory; and no-reflow after opening of the epicardial myocardial artery. The two common denominators of these characteristics are significant microcirculation occlusion and extensive myocardial necrosis^22-23.

Importantly, some patients who arrive early, and many who arrive late, develop massive myocardial loss despite revascularization of the epicardial coronary artery. These patients usually present with TIMI flow grade 0 or 1^{24, 25}. Not uncommonly, the flow after stent implantation is TIMI 2 or less in the absence of optimal myocardial blush^24,25. This phenomenon, known as ‘the no-reflow phenomenon’ is related to the pathophysiology of STEMI. An important observation is that embolization to the downstream microcirculation of micro thrombi and microscopic debris from the ruptured plaque and thrombus occurs as part of the STEMI syndrome. This can transpire many hours before the appearance of STEMI symptoms. A second relevant observation is that microcirculation responds to vasospastic materials released by the thrombus, and prolonged spasm results in very high resistance to flow and possible damage to both endothelial and smooth muscle cells. Third, myocardial edema compresses microcirculation, and prevents flow through microcirculation^26-28. The issue of reperfusion injury has been investigated over the course of many years, and its role in irreversible myocardial damage and clinical practice is yet to be determined despite decades long discussions^29-31.

In addition to its relation to the significant myocardial loss that leads to the development of heart failure, left ventricular remodeling is a secondary process that initially compensates for myocardial loss. However, at later stages, left ventricular remodeling is associated with ventricular enlargement and secondary phenomenon such as functional mitral valve regurgitation. The latter contributes to the reduced capacity of the heart to respond to physiological demands, and thus to worsening of heart failure^17,32,33.

Understanding coronary physiology is key for dealing with STEMI patients at risk for extensive myocardial necrosis. Coronary flow is regulated by myocardial oxygen consumption and can be increased by four-fold in healthy individuals. Increased coronary flow is mandatory for increased oxygen supply to the myocardium, as each molecule of hemoglobin that enters the coronary circulation delivers all the oxygen that is carried during its passage through the myocardium. Thus, only increased flow can provide more oxygen. The rate of flow in the coronary circulation is determined by the intramyocardial resistance of coronary arteries. Vasodilation of these arteries increases coronary flow, which leads to some degree of vasodilation of the epicardial coronary arteries in response to the increased flow. In STEMI, all these physiological mechanisms are disrupted, as detailed above^34-38.

Multiple pharmacological agents and devices have been suggested for reducing myocardial necrosis in STEMI, as add-ons to revascularization^39-41.

The pharmacological agents can be classified as vasodilators, anti-inflammatory drugs, and drugs that play a role at the molecular level.

There are three main classes of devices for reducing myocardial infarct size, which are: 1. devices that unload the left ventricle to reduce oxygen consumption and reduce myocyte injury and necrosis. 2. devices that reduce thrombus load to prevent mechanical occlusion and spasm of the microcirculation and 3. devices that affect microcirculation to improve myocardial perfusion.  A new experimental concept was recently introduced, which entails insertion of an epicardial device to deliver drugs directly to the myocardium, thus potentially reducing infarct size and inducing regeneration in the myocardium⁴².

Ejection fraction is frequently used to assess and predict prognosis after an acute STEMI event. However, more sophisticated parameters such as myocardial perfusion and microcirculatory function, as assessed in the catheterization laboratory or by cardiac MRI, provide higher resolution information on treatment effectiveness, and on pathophysiology and prognosis^15,22. Faster recovery of microcirculation predicts better prognosis of STEMI, and thus provides important insights regarding improving STEMI treatments beyond percutaneous coronary intervention^43-45.

Miracor Medical, a company based in Belgium, explored the novel concept proposed by Prof. Mohl from the University of Vienna, Austria. Prof. Mohl placed a balloon catheter in the coronary sinus and showed that by periodic inflation of the balloon and intermittent occlusion of the coronary sinus is safe and that coronary perfusion can be improved^46,47. Pressure-controlled Intermittent Coronary Sinus Occlusion (PiCSO) technology has been explored in multiple animal models and in several human trials and has received a CE-mark for its use in patients with anterior STEMI presenting with TIMI 0 or 1 within 12 hours of symptom onset. Studies in patients with STEMI demonstrated that the procedure is feasible, safe, there is an improvement in microcirculatory function and a significant reduction in infarct size as shown by MRI^48-50.

The basis of the mechanism of action is that: (1) Occlusion of the coronary sinus causes increased venous pressure, leading to redistribution of coronary flow, with recruitment of collaterals, improved myocardial perfusion and vasodilation of the small arteries and capillaries. (2) Re-opening of the coronary sinus causes a sudden pressure drop, which, in combination with vasodilation leads to a washout and clearance of occluding thrombi and micro-debris. For anterior STEMI, the protocol requires a 30- 45 minute session of PiCSO and is initiated once the culprit lesion has been opened to restore flow. Once running, the PiCSO procedure does not interfere with the intervention in the epicardial coronary artery but addresses the additional reperfusion injury that can be caused by the release of debris that occludes microcirculation during the stenting procedure.

A large-scale, multicenter, multination, randomized study of the use of PiCSO in patients with anterior STEMI presenting with TIMI 0-1 flow is currently ongoing. The primary endpoint is infarct size measured at 5 days after reperfusion by MRI⁵¹.

The heart is a unique organ in many respects since its activity is mandatory to sustain life. The heart’s circulatory system and coronary flow regulation are highly adapted to the vital role of the heart in sustaining life and to everyday physiological challenges.

Understanding coronary physiology is key for treating patients with ischemic heart disease in general, and patients with acute ST elevation myocardial infarction (STEMI) specifically. Coronary flow is regulated by myocardial oxygen consumption and can be increased by four-fold in healthy individuals. The ability to increase coronary flow is referred to as coronary flow reserve. Increased coronary flow is required for increased oxygen supply to the myocardium, as each molecule of hemoglobin that enters the coronary circulation delivers all the carried oxygen during its pass through the myocardium. Thus, only increased flow can provide more oxygen to the heart muscle. Blood flow in the coronary circulation is determined by intramyocardial resistance arteries. Vasodilation of these arteries increases coronary flow, which leads to some degree of vasodilation of the epicardial coronary arteries. In STEMI, all these physiological mechanisms are disrupted. For more details regarding physiology of the coronary system see references^1-5.

The last five decades have witnessed the advent of coronary angiography and physiological measurements of coronary flow in catheterization and experimental laboratories. These have contributed substantial knowledge regarding how myocytes are nourished by the coronary system without disrupting myocardial contraction. While the epicardial coronary arteries, which are demonstrated during coronary angiography, can be regarded as conductance vessels, the resistance vessels that determine blood distribution and flow rate cannot be demonstrated using contrast media. The diameter of these arteries is in the range of 30-500 microns. The endothelial cells that cover the luminal surface of all blood vessels, and the smooth muscle cells that constitute the media layer of blood vessels must operate in synchrony to provide the physiological challenges of normal heart function. Resistance arteries that penetrate the left and right ventricular wall are squeezed during systole; hence, most myocardial blood flow occurs during diastole. The driving force for coronary flow is the gradient of pressures during diastole, between the aorta and the right atrium, which drains most of the coronary flow. Nutrients and gas are exchanged between coronary blood and heart tissue, in the capillaries that connect the arterial and venous system^1,2. Each myocyte is in direct contact with several capillaries, thus securing continuous and sufficient supply of oxygen and nutrients^1,2.

While atherosclerotic plaques are the hallmark of atherosclerosis in the epicardial coronary arteries, dysfunction of microcirculation in the heart, namely malfunctioning resistance arteries and capillaries, plays a major role in chronic syndromes of atherosclerotic heart disease, and even more so in acute coronary syndrome.  Measurement of microvascular resistance is based on thermodilution^6-8. Temperature measurements are taken from the ostium of the coronary artery and the distal coronary artery. These are performed after pharmacological vasodilation is induced by intra-coronary injection of adenosine or papaverine. Pressure and temperature are measured simultaneously in the proximal and distal coronary artery using a pressure wire; the procedure requires only a few minutes. Microcirculatory resistance is calculated using Ohm’s law V=IR, in which V equals the pressure gradient between the distal coronary artery and the pressure in the venous system that drains the coronary flow. Coronary flow is measured using thermodilution and is denoted as I in the equation, and R is the resistance. The index of microcirculatory resistance (IMR) can be calculated after measuring the index distal coronary pressure and index coronary artery flow (the venous pressure is relatively low and considered to be zero), using the equation IMR=index distal coronary artery pressure/index coronary artery flow. Several technical issues must be considered in measuring IMR, but these issues are beyond the scope of this document. More details on measuring IMR can be found in references (6-12). Normal IMR is defined as IMR<20 units. IMR>25 units is considered abnormally high and an indication of disturbances to coronary flow. Continuous coronary resistance is also possible and normal values are defined as <450 woods units^12-14.

A second major method to measure coronary microcirculation function is by cardiac magnetic resonance. Contrast echocardiography, Doppler echo, CT, and PET are also currently used to assess microcirculation in the heart¹⁵.

For many years, the driver-regulator of arterial vasodilation in the myocardium was unknown. An oxygen sensor element was recently identified in smooth muscle cells of coronary resistance arteries¹⁶. When oxygen consumption exceeds oxygen supply, reduced myocardial oxygen tension leads to vascular dilation and increased coronary flow. Endothelial cells in the microcirculation and epicardial coronary have flow sensing elements¹⁷. With increased flow following dilation of resistance arteries, these cells secrete nitric oxide, which enhances vasodilation and increases coronary flow.

The importance of coronary microcirculation in STEMI cannot be understated. Ample evidence indicates that the return to normal of microvascular flow after myocardial infarction is an excellent predictor of short- and long-term prognosis and of left ventricular recovery. Patients with STEMI who have disturbed microcirculation (increased resistance) after angioplasty develop late complications, mostly heart failure, at higher rates than do patients with STEMI with functioning microcirculation (normal resistance) after angioplasty^18-22.

There is a clear relationship between the time between onset pf symptoms and revascularization to the short- and long-term outcome of STEMI and many patients who arrive late to the catheterization laboratory after the onset of STEMI symptoms develop massive myocardial loss. A minority of patients who arrive early may also suffer from massive myocardial loss. These two groups of patients usually present with TIMI flow grade 0 or 1 and in many instances, flow after stent implantation is TIMI 2 or lower^23,24. Several explanations are possible for this phenomenon, which is related to the pathophysiology of STEMI^25-27. First, embolization of downstream microcirculation with micro thrombi and microscopic debris from the ruptured plaque is integral to the STEMI syndrome. Notably, embolization can occur several hours or days before onset of STEMI symptoms. Second, the microcirculation responds to vasospastic materials that are released by the thrombus; the prolonged spasm results in very high resistance to flow and possibly damages both endothelial and smooth muscle cells. Third, myocardial edema compresses microcirculation and prevents flow through microcirculation. In addition to the three mechanisms delineated above, the role of reperfusion injury in irreversible myocardial damage has been investigated over many years, and optimal clinical practice is yet to be determined.

Multiple pharmacological interventions are advocated to alleviate microcirculatory dysfunction in patients with STEMI²⁸, among them, intracoronary adenosine and nitroglycerine injection; however, their effects are usually short term. Heparin, anti-platelet aggregation drugs, and thrombolytic therapy also contribute to normalization of microcirculation in patients with STEMI, but these cannot be effective in blood vessels with no sustained flow, as in the event of STEMI^28-29.

Devices to treat patients with STEMI are directed to unload the left ventricle and reduce afterload, and hence reduce myocardial oxygen consumption, to aspirate epicardial coronary thrombus^30,31. However, in large scale studies, these devices were not shown so far to have a beneficial effect on prognosis.

Currently, the only device directed at microcirculatory perfusion is the Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) system, developed by Miracor, a company based in Belgium^32-36. This device explores the novel concept espoused by Prof. Mohl from the University of Vienna, Austria. Accordingly, a balloon catheter is placed in the coronary sinus of patients with anterior STEMI; the balloon is periodically inflated and the coronary sinus thereby intermittently occluded. Prof. Mohl showed that this system can improve coronary microcirculatory perfusion and achieve myocardial salvage.

The PiCSO therapy has been explored in multiple animal models and in several human trials and received CE mark for its use in patients with anterior STEMI. PiCSO therapy is started after restoration of flow in the epicardial artery and during stenting. The PiCSO procedure therefore does not interfere with the intervention in the epicardial coronary artery^31-33. The mechanism of action involves three basic consequences of intermittently occluding the coronary sinus:

1. The pressure in the coronary microcirculation is increased and the size of the small arteries and capillaries is enlarged. Larger size enables clearance of occluding thrombi and debris, and results in better flow during PiCSO balloon deflation.
2. The increased coronary sinus pressure leads to redistribution of coronary flow, with recruitment of collaterals and improved myocardial perfusion. In anterior STEMI, the protocol requires a 20-60-minutes of PiCSO.
3. In addition to the mechanistic effects, recent studies showed that the PiCSO treatment leads to the release of several cytokines and small RNAs that are associated with myocardial regeneration.

Currently, a large-scale, multicenter, multination, randomized study of the use of PiCSO in patients with anterior STEMI presenting with TIMI 0-1 flow is ongoing. The primary endpoint is infarct size measured by cardiac MRI at 5 days after reperfusion.

The prior experience of both distributors in introducing novel technologies with the requisite focus on physician training, and a measured commercial approach through highly qualified centers of excellence, was a key factor in their assignment. Since receiving the CE-Mark in 2020, Miracor’s European commercial strategy in 2021, has been focused on a limited market introduction while the pivotal European randomized trial (PiCSO-AMI-I) finalizes recruitment. By building the strong foundations of success in a small number of expert hospitals in key geographies, Miracor intend to broaden the launch in 2022 and beyond, in parallel with further trials in the USA, and in Europe and the Nordic region.

PiCSO is an innovative medical device designed to improve the outcomes and quality of life of patients presenting with acute myocardial infarction with elevation of the ST segment (STEMI).

The PiCSO Impulse system is composed of: 

• The PiCSO Impulse Console, monitoring the procedure and tracking the coronary sinus pressure; 
• The PiCSO Impulse Catheter (8Fr), inserted through a femoral vein to access the coronary sinus; 
• Some detachable components including a Coronary Sinus pressure cable, an ECG cable and a helium gas cartridge. 

The PiCSO benefits:

PiCSO reduces infarct size and improves clearance of the microcirculation in STEMI patients by intermittently occluding the coronary sinus during Primary PCI. This intermittent occlusion allows the redistribution of blood flow from normal perfused areas to deprived myocardium, the clearing of microvascular obstruction as well as an enhanced washout of deleterious agents from the microcirculation.  

If you have interest in learning more about PiCSO, please complete the following form or reach out directly to GADA Italia (marketingcvs@gadagroup.com) or New Medical Solutions (Puglia).

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).

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’.

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.

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.

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.