Article
Debate
REC Interv Cardiol. 2019;1:51-53
Debate: MitraClip. The heart failure expert perspective
A debate: MitraClip. Perspectiva del experto en insuficiencia cardiaca
aServicio de Cardiología, Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, Valencia, Spain bCIBER de Enfermedades Cardiovasculares (CIBERCV), Spain
Related content
Debate: MitraClip. The interventional cardiologist perspective
QUESTION: How often do you see nonrevascularizable patients with refractory angina today?
ANSWER: The prevalence of this complex entity has gone up thanks to the better prognosis of patients with ischemic heart disease due to changes of lifestyle, drugs, and coronary interventions. Among these, surgical revascularization and, in particular, percutaneous coronary interventions increase survival in the acute coronary syndrome setting. For its diagnosis, reversible myocardial ischemia that cannot be controlled with a combination of medical therapy, angioplasty, and myocardial revascularization surgery needs to be documented first. Although it is often due to severe stenosis of epicardial coronary arteries, it can be seen in non-atherosclerotic coronary artery diseases (spasm, microvascular disease, etc.) and myocardial diseases within the heart-brain axis including myocardial metabolism, and coronary microcirculation. Also, in the perception of pain until neuromodulatory pathways that can also be therapeutic targets in this clinical condition. Therefore, obstructive coronary disease is only one of the possible phenotypes in patients (women in particular) with angina or myocardial ischemia. There is no clear evidence associated with a higher mortality rate; however, the quality of life of rehospitalized patients is worse and health costs are higher.1,2 Former studies1,3 describe a prevalence of refractory angina (RA) of 5% to 10% in patients with chronic coronary syndromes; these studies often focus on nonrevascularizable patients with angina on non-optimized antianginal drug therapy excluding patients without stenosis of epicardial coronary arteries. These studies do not report either on possible cases of RA due to coronary microvascular dysfunction that actually seem to be most of the patients with RA.
Q.: Please explain to us briefly the diagnostic approach used for screening etiologies different from ischemia due to epicardial coronary artery disease such as microvascular ischemia, vasospasm or even noncardiac causes.
A.: Beyond the traditional idea of ischemia-angina where imbalance between myocardial oxygen supply and demand is the main pathophysiological mechanism, we should admit that, in many cases, ischemia is not followed by angina and that many ischemic patients have a constellation of symptoms that may worsen their quality of life.
To improve quality of like is the primary endpoint in patients with angina in the chronic ischemic heart disease setting since its presence or myocardial ischemia do not seem to increase mortality. In this sense, rather than making us question the prognostic value of systematic myocardial revascularization in patients with angina in the chronic coronary syndrome setting, the recent results of the ISCHEMIA clinical trial4 should make us think of the need to conduct routine tests to detect ischemia. In this study, over 20% of the selected patients with angina/ischemia could not be randomized eventually for the lack of significant coronary stenoses. In this sense, it has been reported that nearly 40% of the patients with angina without coronary stenosis showed vasomotor response disturbances in coronary micro and macrocirculation. On the other hand, we should transcend the idea of hypoperfusion as the cause of angina and myocardial ischemia; the metabolic alterations of cardiomyocytes related to hypoxia can be due to peaks in the ischemia threshold as the adaptation of metabolism to hypoperfusion or decrease in metabolic situations of use of substrates of lower energy efficiency.1
The diagnosis of microvascular angina is often achieved after discarding significant epicardial coronary stenosis; since segmental contractility alterations are rare on these patients’ exercise echocardiography, we need specific techniques to assess coronary circulation/perfusion and confirm the diagnosis.
I’d like to add that angina, including RA, in the absence of significant coronary stenosis cannot be a diagnosis of exclusion. New protocols are needed to confirm not only the clinical signs and ischemia, but also the pathophysiological mechanisms involved. Only then the diagnostic and therapeutic strategy will be complete for each particular case.
Q.: Which are the best pharmacological strategies to treat refractory angina and how should drug escalation be done?
A.: I think that changing our management of nonrevascularizable patients with RA to improve their clinical situations is a priority. These patients often remain in some sort of diagnostic and therapeutic limbo. Disease exists beyond the possibilities of coronary dilatation. Therefore, only by knowing the pathophysiological substrate of angina in each particular case, we’ll be able to establish protocols including new therapeutic, pharmacological or other modalities.5
The standard of care for the management of patients with RA is to discard and treat secondary causes by optimizing medical therapy and rehabilitation. These patients should be treated with antianginal drug therapy, beta-blockers, dihydropyridine calcium channel blockers, and sustained-release nitrates. In cases of persistent angina, ivabradine can be used in patients who are in sinus rhythm with heart rates ≥ 70 beats/minute. Also, the possible combination of ranolazine, trimetazidine, and nicorandil is another antianginal therapeutic option. Patients with RA without obstructive coronary lesions benefit from a better control of their angina when therapy is based on every particular patient and the results of intracoronary functional tests. Patients with microvascular angina, reduced coronary flow reserve, increased resistances, and a negative acetylcholine testing respond positively to treatment with beta-blockers, angiotensin-converting enzyme inhibitors, and statins. They are also responsive to rehabilitation programs to control their risk factors, physical exercise, and weight loss. Patients with EKG changes and angina as a response to the acetylcholine testing but without epicardial coronary spasm should be treated as if they had vasospastic angina: dihydropyridine calcium channel blockers and sustained-release nitrates are the drugs of choice associated with changes in the patient’s lifestyle and control of their risk factors. Data available today show the efficacy of ranolazine plus traditional antianginal drugs in patients with microvascular angina; due to its mechanism of action, it should be considered a supplementary therapeutic option in this group of patients
Q.: Which non-invasive, non-pharmacological alternatives exist for these patients?
A.: As I already mentioned, patients with RA should join structured cardiac rehabilitation programs to change their lifestyle. Exercise adapted to each particular case has proven to improve ischemia and stimulate collateral circulation, coronary vascular function, and control the main cardiovascular risk factors. To control the symptoms, transcutaneous electrical nerve stimulation has been suggested. Extracorporeal shock waves can promote myocardial revascularization, and external counterpulsation generates diastolic retrograde aortic flow that increases the coronary diastolic and mean pressures. Also, retrograde flow improves myocardial perfusion after inducing flow-mediated coronary vasodilation and stimulates angiogenesis. There is not a single solid piece of evidence on the utility of these techniques in patients with RA. Actually, they should be used based on each particular case strictly as compassionate use and only when the remaining therapeutic options have failed.1
Q.: What evidence do we have today on the Reducer device?
A.: Several invasive techniques have been developed to improve angina including neural stimulation, stellate ganglion block, myocardial laser revascularization, angiogenic stimulation with plasmid DNA, and implantation of CD34+ and CD133+ cells. The results of a recent meta-analysis on the intramyocardial injection of CD34+ have confirmed that it improves angina, the patients’ functional capacity, and prognosis. However, for the time being these techniques are in research stage only.1
The description that an increased coronary sinus pressure induces myocardial flow redistribution in the ischemic regions of patients with RA is the basis of the Reducer device design (Neovasc Inc., Canada). It is a metal balloon-expandable percutaneous device that causes the focal the stenosis of coronary sinus rising its pressure and elevating it in the venules and capillaries too. This promotes the redistribution of flow bringing the endocardial/epicardial perfusion gradient back to normal.1 Several studies confirm the safety profile of this technique and its benefits regarding symptom improvement; the early study results of 15 patients confirmed its long-term safety profile with 12-year patency in 10 of these patients and symptom improvement. However, device migration and coronary sinus perforation and bleeding have been reported; these are complications that should be taken into consideration when giving this device a clinical use. From my own point of view, the only randomized clinical trial published to this date, the COSIRA (Coronary sinus reducer for treatment of refractory angina)6 offers modest efficacy results. A total of 104 patients with RA were randomized to receive the Reducer device or undergo a sham procedure. The patients who received the device improved their angina symptoms and quality of life. However, no significant changes were seen in the stability and frequency of angina or in the duration of exercise.
Several real-world registries confirm the efficacy and safety profile seen in the clinical trial with maximum clinical benefits reported after 4 months and maintained at the 2-year follow-up.7 Improvements in inducible ischemia, functional capacity in the cardiopulmonary exercise testing, myocardial perfusion, and cardiac function have been reported. A special comment should be made on symptom efficacy and myocardial perfusion with the Reducer device in 8 patients with microvascular angina.1
Considering the time elapsed since the arrival of the Reducer device and the scarce quality of scientific evidence with just one randomized clinical trial available and a very qualitative primary endpoint (the assessment of the patient’s self-reported angina), in my opinion, at least, 2 clinical trials should be conducted: the first one in patients with RA due to nonrevascularizable coronary lesions. The second one in patients with microvascular angina. The first study primary endpoint should include symptom improvement according to some objective test of overload and myocardial perfusion assessed through cardiac magnetic resonance imaging. The second study primary endpoint should also include these components plus the functional assessment of coronary microcirculation. In the meantime, I think it should only be used as compassionate use in quality high-volume PCI-capable centers for the management of patients with RA on an optimized therapeutic strategy and clinical follow-up including objective tests to assess ischemia and myocardial perfusion.
FUNDING
No funding was received for this work.
CONFLICTS OF INTEREST
The authors declare no conflicts related to this work.
REFERENCES
1. Gallone G, Baldetti L, Tzanis G, et al. Refractory angina. From pathophysiology to new therapeutic nonpharmacological technologies. JACC Cardiovasc Interv. 2020;13:1-19.
2. Lanza GA, Crea F, Kaski JC. Clinical outcomes in patients with primary stables microvascular angina:is the jury still out?Eur Heart J Qual Care Clin Outcomes. 2019;5:283-291.
3. Sara JD, Widmer RJ, Matsuzawa Y, Lennon RJ, Lerman LO, Lerman A. Prevalence of Coronary Microvascular Dysfunction Among Patients With Chest Pain and Nonobstructive Coronary Artery Disease. JACC Cardiovasc Interv. 2015;8:1445-1453.
4. Maron DJ, Hochman JS, Reynolds HR, et al. Initial Invasive or Conservative Strategy for Stable Coronary Disease. N Engl J Med. 2020;382:1395-1407.
5. Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41:407-477.
6. Verheye S, Jolicœur EM, Behan MW, et al. Efficacy of a device to narrow the coronary sinus in refractory angina. N Engl J Med. 2015;372:519-527.
7. Giannini F, Baldetti L, Ponticelli F, et al. Coronary Sinus Reducer Implantation for the Treatment of Chronic Refractory Angina:A Single-Center Experience. JACC Cardiovasc Interv. 2018;11:784-792.
QUESTION: How often do you see nonrevascularizable patients with refractory angina today?
ANSWER: Refractory angina is defined as chronic angina that cannot be controlled even with the use of optimal medical therapy and where all revascularization options have failed.1,2 It is a common entity whose prevalence is on the rise due to the ageing of population and the improved prognosis of ischemic heart disease. It is estimated that between 5% and 10% of the patients with chronic ischemic heart disease can develop refractory angina. Its annual incidence rate is between 50 000 and 100 000 cases in the United States and between 30 000 and 50 000 cases in Europe.1,2 On the other hand, we know that around 10% of all coronary angiographies performed indicate that it is not possible to give efficient options of revascularization. According to the activity registry in interventional cardiology in Spain from 2019,3 this figure would be up to 15 000 patients each year, and it is reasonable to think that a significant percentage can suffer refractory angina.
These patients often remain asymptomatic which negatively impacts their quality of life and. Actually, to this day, we still do not have effective therapeutic options to offer. Multidisciplinary approach is crucial here (cardiology, family medicine, cardiac rehabilitation, psychology, pain management units, etc.). Also, we should consider the use of non-pharmacological therapies like spinal cord or subcutaneous stimulation, external counterpulsation or use the coronary sinus reducer device as well as keep looking into other alternatives like new drugs, cardiac shock wave therapy or use of progenitor cells.1,2
Q.: Please explain to us briefly the diagnostic approach used for screening etiologies different from ischemia due to epicardial coronary artery disease such as microvascular ischemia, vasospasm or even noncardiac causes.
A.: The diagnosis of refractory angina is mainly clinical, but it is important to show that there is a correlation between symptoms and ischemia. That is why it is essential to confirm the presence of myocardial ischemia, if possible, through imaging modalities like stress echocardiography, pharmacological stress echocardiography, single-photon emission tomography or magnetic resonance imaging. If no ischemia is seen on these imaging modalities, other possible causes for the symptoms should be considered like esophageal spasm or osteomuscular etiology. In the presence of ischemia, we need to know the coronary anatomy preferably through a coronary angiography before discussing any revascularization options. Information should be analyzed by the heart team including experienced interventional cardiologists and cardiac surgeons to determine the possibilities of percutaneous or surgical revascularization.
There are 2 groups of patients without revascularization options: the largest one, with advanced coronary disease (diffuse disease, small-caliber distal beds, chronic total coronary occlusions non-eligible for percutaneous coronary intervention, coronary artery bypass graft deterioration…); and that of patients with angina and myocardial ischemia without obstructive coronary lesions. In these patients it would be good to perform a functional study with microvascular dysfunction and coronary spasm testing (coronary reserve, index of microvascular resistance, absolute coronary flow, acetylcholine test) to facilitate targeted therapies with better symptom control.
Q.: What evidence do we have today on the Reducer device?
A.: It is a new option for patients with refractory angina with a different mechanism of action over the cardiac venous system. This mechanism developed over 60 years ago by Claude S. Beck4 is based on creating coronary sinus (CS) stenosis to generate a pressure gradient that is transmitted retrogradely to venules and capillaries, which translates into an improved subendocardial perfusion, probably due to collateral recruitment through the venous plexus and Thebesian veins.
The first experience with humans was reported back in 2007. In 2015 the COSIRA multicenter, randomized, double-blind, sham-controlled clinical trial5 was published. It included a total of 104 patients with refractory angina and functional class III or IV according to the Canadian Cardiovascular Society (CCS) with ischemia seen on the dobutamine stress echocardiography and without any revascularization options after assessment by the medical team assessment. The primary endpoint was to reduce, at least, 2 CSS functional class degrees of severity of angina at the 6-month follow-up. The Reducer device was superior to the sham procedure (35% vs 15%; P = .024), improved, at least, 1 CSS functional class degree of angina in 71% of the patients vs 42%, and improved parameters like duration of exercise or quality of life.
Also, there is evidence of the results of the REDUCE registry6—similar to those reported by the COSIRA trial—in the routine clinical practice on the improvement of, at least, 1 CSS functional degree of angina in 81% of the patients, better parameters of quality of life, greater distances covered in the six-minute walk test, and lower the need for antianginal drugs. The REDUCER-1 registry results of 195 patients presented at Euro-PCR 2019 showed that clinical benefit remained at the 2-year follow-up.7
Overall, in all the studies published it was effective in up to 75% of the patients.8 The reasons why some patients remain unresponsive to therapy are still not known, but they could be associated with lack of device endothelization or with an alternative venous drain through other territories.
An important conclusion we can draw from the accumulated experience is that the implantation of the Reducer device is viable and safe5-8 with serious complications (like CS dissection or perforation or device embolization) in less than 2% of the cases. The 10-plus-year follow-up of the early patients has confirmed its patency and lack of structural alterations in the long-term. No CS thrombosis has ever been reported after implantation.
Magnetic resonance imaging study supports the hypothesis of an increased subendocardial perfusion as the mechanism of action by showing that in ischemic areas the correlation between the myocardial perfusion reserve index and the endocardial reserve index—that remains low at baseline—increases after implantation. Also, myocardial perfusion improves when reducing the myocardial ischemic burden, improving the longitudinal and circumferential strain and systolic function without microstructural alterations or effect on the diastolic function.9
With the accumulated evidence, the last clinical practice guidelines on the management of chronic coronary occlusions of 2019 established by the European Society of Cardiology (ESC) included, for the very first time, the implantation of the Reducer device in patients with refractory angina with the same level of recommendation (IIb, level of evidence B) than other previous non-pharmacological options like external counterpulsation or spinal cord stimulation.10
Q.: How is the selection process of the most eligible candidates for this technique?
A.: In my opinion, most patients with symptomatic refractory angina are potential candidates despite the optimal medical therapy without percutaneous or surgical revascularization options after assessment by the heart team and with myocardial ischemia in the left main coronary artery territory as seen on the imaging modalities.6 Due to vein drain anatomy of the right coronary artery territory through the middle and small cardiac veins that drain into the CS very close to its ostium, this drainage would not be affected by the implant. For this reason, the Reducer device would not be the right option for patients with ischemia in the right coronary artery territory only. Thanks to its mechanism of action, it may be an interesting option for patients with ischemia due to microvascular disease without lesions in the epicardial coronary arteries. Although information is still limited in this context information, the early data are positive.11
One contraindication would be the presence of left ventricular pacing electrodes through the CS for resynchronization purposes, which is why its indication should be carefully studied in patients with ventricular dysfunction who may be candidates to such therapy.
Patients with refractory angina can also be candidates to other non-pharmacological therapies like external counterpulsation or neurostimulation. Although they have been available for decades, these techniques have been underused for different reasons like the perception of the lack of efficacy or placebo effect or lack of solid scientific evidence. Randomized clinical trials are needed to compare these different techniques and establish the best way to approach the management of these patients.
Q.: Can you please give us a brief technical description of this procedure?
A.: The implantation of the Reducer device is easy on the technical level12,13 and successful in over 95% of the cases. The device is implanted under local anesthesia via right jugular vein as the access of choice and preferably under vascular ultrasound guidance. A 6-Fr introducer sheath is used followed by the advancement of a multipurpose catheter until the right atrium while keeping the mean pressure < 15 mmHg (with higher pressures the implantation is ill-advised since the pressure of the CS is already high at the baseline level). Afterwards, the CS undergoes selective catheterization by carefully advancing the multipurpose catheter and avoiding small-caliber branches like the left marginal ones or the vein of Marshall. There are times that a highly developed or fenestrated Thebesian valve can make selective catheterization difficult. A venography of CS is performed through the multipurpose catheter to see its size, the origin of lateral branches, and the presence of valves (like Vieussens valve that can complicate the implant).
If the procedure is continued, heparin is administered, and the guidewire is placed distal to the CS. Then, the introducer sheath is changed for a 9-Fr sheath to advance the guide catheter and deliver the device in the location previously indicated by the venography (2-4 cm from the origin of CS avoiding the jailing of lateral branches). The device consists of a stainless-steel balloon-expandable stent whose balloon has the shape of a sand clock that leaves a central waist of 3 mm. It is implanted through the inflation of a second balloon for 30 to 60 seconds at 4 to 6 atm, adjusting its size to the actual diameters of CS of 9.5 mm to 13 mm. During inflation oversizing is attempted (10% to 20%) to reduce the risk of embolization and facilitate neointimal coverage. Once implanted, the balloon is carefully removed until the guide catheter making sure that the Reducer device remains stable. Lastly, a new venography is performed to check the position of the device and lack of complications. The patient can be discharged early on after the procedure and dual antiplatelet therapy is advised for, at least, a month. The effect is evident with device endothelization, which creates a coronary sinus (CS) stenosis, which is why it is necessary to wait between 4 and 6 weeks to determine its efficacy.
In conclusion, the CS Reducer device is a new technique for the management of refractory angina. It improves myocardial perfusion acting from the cardiac venous system. Clinical results confirm its efficacy and safety profile, the technique is easy to use, and its indication has already been established in the clinical practice guidelines. Clinical evidence still needs to grow with more patients, longer follow-up periods, comparisons to other therapies, and further research on the mechanisms of nonrespondent patients. Nonetheless, the Reducer device is a new tool in the interventional cardiology armamentarium that can be an option for patients with refractory angina without revascularization options.
FUNDING
No funding.
CONFLICTS OF INTEREST
None declared.
REFERENCES
1. Gallone G, Baldetti L, Tzanis G, et al. Refractory Angina:From Pathophysiology to New Therapeutic Nonpharmacological Technologies. JACC Cardiovasc Interv. 2020;13:1-19.
2. Sainsbury PA, Fisher M, de Silva R. Alternative interventions for refractory angina. Heart. 2017;103:1911-1922.
3. Ojeda S, Romaguera R, Cruz-González I, et al. Registro Español de Hemodinámica y Cardiología Intervencionista. XXIX Informe Oficial de la Asociación de Cardiología Intervencionista de la Sociedad Española de Cardiología (1990-2019). Rev Esp Cardiol. 2020;73:927-936.
4. Beck CS, Leighninger DS. Scientific basis for the surgical treatment of coronary artery disease. J Am Med Assoc. 1955;159:1264-1271.
5. Verheye S, Jolicoeur EM, Behan MW, et al. Efficacy of a device to narrow the coronary sinus in refractory angina. N Engl J Med. 2015;372:519-527.
6. Giannini F, Baldetti L, Konigstein M. Safety and efficacy of the reducer:A multi-center clinical registry REDUCE study. Int J Cardiol. 2018;269:40-44.
7. EuroPCR 2019. A proven evidence-based therapy when angina persists. Reducer I Registry. Verheye S. Available online: https://www.pcronline.com/. Accessed 8 Sep 2020.
8. Konigstein MN, Giannini F, Banai S. The Reducer device in patients with angina pectoris:mechanisms, indications, and perspectives. Eur Heart J. 2018;39:925-933.
9. Palmisano A, Giannini F, Rancoita P, et al. Feature tracking and mapping analysis of myocardial response to improved perfusion reserve in patients with refractory angina treated by coronary sinus Reducer implantation: a CMR study. Int J Cardiovasc Imaging. 2020. http://dx.doi.org/10.1007/s10554-020-01964-9.
10. Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41:407-477.
11. Giannini F, Baldetti L, Ielasi A, et al. First Experience With the Coronary Sinus Reducer System for the Management of Refractory Angina in Patients Without Obstructive Coronary Artery Disease. JACC Cardiovasc Interv. 2017;10:1901-1903.
12. Giannini F, Aurelio A, Jabbour RJ, et al. The coronary sinus reducer:clinical evidence and technical aspects. Expert Rev Cardiovasc Ther. 2017;15:47-58.
13. Giannini F, Tzanis G, Ponticelli F, et al. Technical aspects in coronary sinus Reducer implantation. EuroIntervention. 2020;15:1269-1277.
QUESTION: Do you think there is enough evidence to indicate the use of intravascular imaging during percutaneous coronary interventions?
ANSWER: Currently, there is enough evidence on the benefits provided by intracoronary imaging modalities during percutaneous coronary interventions. Actually, the clinical practice guidelines recommend their use. For the most part, evidence has been collected on the use of these imaging modalities to optimize angioplasty. In this sense, the 2018 guidelines on revascularization published by the European Society of Cardiology give a class IIa recommendation and a grade B level of evidence to the use of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) for the optimization of percutaneous coronary interventions (PCI) in selected patients.1 In the case of IVUS, these recommendations are based on multiple studies and meta-analyses that compared the results of angiography vs IVUS-guided PCIs and showed fewer events (including death, infarction or need for new revascularization) with the use of intravascular imaging modalities.2 Guidelines make a specific recommendation on the use of IVUS while performing an angioplasty on the left main coronary artery (class IIa, grade B level of evidence). The other indication for intracoronary imaging modalities established in the guidelines on revascularization is stent failure (class IIa, grade C level of evidence). Several observational studies have proven the utility of IVUS and OCT to detect the causes of thrombosis and restenosis and guide percutaneous treatment.
Q.: Which are the anatomical or clinical contexts with more evidence available?
A.: As I said the clinical context with more evidence available today is the optimization of coronary angioplasty with numerous randomized clinical trials and meta-analyses that confirm the occurrence of fewer events with IVUS-guided PCIs. This effect is especially relevant in the subgroup of patients with complex lesions (including long lesions, bifurcations, and chronic total coronary occlusions) who have a higher risk of events. During the PCI, imaging modalities allow us to determine the size of the stent, optimize its implantation, guarantee its adequate expansion and apposition, and detect possible complications like border dissections.2
The second context with more evidence available (in this case from observational studies) is stent failure. Regarding restenosis, imaging modalities can provide information on its causes (neointimal growth, neoatherosclerosis, underexpansion, disease progression in the stent borders) to determine the most appropriate treatment. Regarding stent thrombosis, intracoronary imaging modalities can detect whether stent thrombosis is due to mechanical causes (like stent underexpansion or incomplete apposition). Also, the OCT allows us to determine whether the cause is associated with an inadequate neointimal coverage of the struts or the rupture of a plaque at the borders or inside the stent.
The anatomical location with highest consensus of all regarding the advantages of using intracoronary imaging modalities (IVUS in particular) is the left main coronary artery. Several studies have proven the utility of this imaging modality to determine the severity of stenosis, the need for revascularization, and eventually to optimize angioplasty.
Q.: Is the IVUS and OCT level of evidence the same?
A.: Since the IVUS has been used much longer than the OCT, there are more clinical studies available on the use of the former, especially as an angioplasty guided imaging modality (to determine the size of the stent and optimize its implantation). However, 2 studies have proven the non-inferiority of OCT vs IVUS for the optimization of stent implantation. The ILUMIEN III study randomized 450 patients who received an OCT, IVUS or angiography-guided angioplasty. It proved the non-inferiority of OCT vs IVUS regarding the minimum stent area obtained. The OPINION study, conducted in Japan, randomized 829 patients to OCT or IVUS-guided stent implantation and proved the non-inferiority of OCT vs IVUS in the primary endpoint of target vessel failure including cardiac death, treated vessel related infarction or new revascularization on the lesion operated on. This prompted that the latest iteration of the revascularization guidelines published by the European Society of Cardiology to give the same class of recommendation (IIa) to the use of IVUS and OCT for PCI optimization.
Q.: What are the advantages of OCT with respect to IVUS during percutaneous coronary interventions?
A.: The OCT has 10 times more resolution than the IVUS, which allows much more detailed visualizations of the arterial wall and its interaction with the stent. This makes it much more sensitive to detect phenomena like stent incomplete apposition or stent border dissection. In the long-term assessment of the stent it also allows us to study the vessel tissue repair and determine whether the stent is completely covered by tissue. Regarding acute coronary syndromes, the OCT is much more sensitive to detect the presence of thrombi and it can characterize the underlying cause much better. In this sense, the OCT allows us to distinguish in vivo acute coronary syndromes due to the rupture of the plaque from those due to erosions, calcified nodules or non-atherosclerotic causes (such as spontaneous coronary artery dissections or embolizations). This is relevant to guide treatment because it can determine whether it is necessary to operate or just use conservative strategy.3
Also, the OCT offers several advantages in the assessment of the causes of stent failure. Regarding in-stent restenosis, it allows us to detect its underlying mechanisms like underexpansion, neointimal tissue growth or disease progressions. Also, the high resolution of this imaging modality has enabled the in vivo detection of neoatherosclerosis as a common cause for restenosis. The analysis of these mechanisms is essential to determine the best therapeutic strategy. For example, in the case of disease progression in the borders of the stent it will be necessary to implant a new stent. However, in cases of stent underexpansion it will be necessary to expand the stent with high pressure dilatations, in some cases, even use plaque modification techniques. If the cause of restenosis is neointimal growth a new stent or a drug-coated balloon can be implanted. Regarding neoatherosclerosis, at the moment there is not enough evidence to determine whether the best strategy is to implant a new stent or use a drug-coated balloon. Still, some data available suggest that both options may be useful.
Regarding stent thrombosis, the OCT allows us to demonstrate in vivo that this is often a multifactor phenomenon and that the cause is not only the lack of stent coverage (as it was initially thought with drug-eluting stents). Instead, it can be due to other factors like neoatherosclerosis with plaques ruptured inside the stent or around its borders, stent underexpansion, incomplete apposition or restenosis. Again, this is an important piece of information to guide the interventional treatment and correct the underlying cause.
Q.: Which cases would be eligible for using IVUS and which for using OCT?
A.: There are 2 anatomical locations where the IVUS is superior compared to the OCT: 1) ostial lesions, due to the impossibility to clean out the blood from the vessel to acquire good images on the OCT; and 2) the left main coronary artery, especially when the ostial segment is involved. Before, the size of the left main coronary artery was a limitation when performing OCT, but with the systems we have today we can see almost all left main coronary arteries unless they are too big. Several studies show the utility of IVUS to assess the severity of the left main coronary artery and for guidance purposes during the angioplasty. At this moment, several studies in the pipeline are assessing the use of OCT while performing angioplasties on the distal left main coronary artery. Probably in the mid and distal left main coronary artery setting, the OCT will be as useful as the IVUS. Maybe even more in the assessment of bifurcations. However, if the ostial segment is involved and we want to see it, we better use the IVUS. Another situation where the IVUS may be preferred over the OCT is to see kidney damage given the need to use contrast for the acquisition of OCT images. In this sense, I should say that the use of contrast can be optimized when performing OCT-guided angioplasties to avoid unnecessary angiographies. A single injection of contrast allows us to perform an angiography and an OCT at the same time. With a single OCT-pullback the reference areas can be selected, and the diameter and length of the vessel can be obtained avoiding the need to perform multiple angiographies.
The OCT is superior to the IVUS and should be the imaging modality of choice to assess stent failure (thrombosis and restenosis) because it is much more precise to determine the underlying mechanism. It is also superior for the assessment of acute coronary syndromes because it is much more sensitive to detect thrombi and distinguish acute coronary syndromes due to plaque rupture from those due to other mechanisms like erosions or non-atherosclerotic causes. The OCT is superior to the IVUS for the assessment of bifurcations because it allows online 3D reconstructions that provide relevant information on the anatomy of the bifurcation and can optimize the angioplasty. An important advantage of the OCT over the IVUS conventional systems is the possibility of a simultaneous registry with an angiography incorporated to the system that does not require the use of any additional software. This facilitates significantly the use of OCT to guide and optimize stent implantation because it offers an online co-registration of the angiographic location of each and every one of the images seen on the OCT.
Q.: What studies are necessary to establish the role of these imaging modalities during percutaneous coronary interventions?
A.: Regarding IVUS, several studies show that its use during the angioplasty can improve the prognosis of patients by reducing the occurrence of events. Regarding the OCT, the primary endpoint of the ILUMIEN IV study, currently in the pipeline, is to show that OCT-guided PCIs can improve stent implantation and reduce clinical events compared to angiography-guided PCIs only. The positive effects of using intracoronary imaging modalities are especially relevant in the subgroup of lesions with higher risk of failure (including long lesions, bifurcations, restenosis, and chronic coronary occlusions). Actually, it is in these patients in whom we should encourage the use of IVUS or OCT.
Beyond the evidence generated in the clinical trials, in order to promote the use of intracoronary imaging modalities, interventional cardiologists need to be trained on how to interpret them. At the same time, imaging systems need to improve to make them easier to use during the procedures. For example, the use of fast systems of image acquisition integrated in the cath lab that allow the operator to use the controls from the table, and co-registration of angiography are some of the tools that can improve the use of these imaging modalities.
Q.: What technical advances are available today or could be available in the near future regarding the OCT?
A.: Among the technical advances currently under research, the most relevant ones have to do with the possibility of estimating and assessing the physiological parameters from OCT acquired 3D reconstructions. This would allow us to use 1 imaging modality only (the OCT) to determine the need to treat and optimize the intervention.
Plaque characterization (especially calcium) using dedicated software is another important field of study. Ultrafast pullbacks will allow us to reduce the amount of contrast needed, and the combination of IVUS plus OCT in the same catheter are other advances being made today.
REFERENCES
1. Neumann F-J, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019;40:87?165.
2. Räber L, Mintz GS, Koskinas KC, et al. Clinical use of intracoronary imaging. Part 1:guidance and optimization of coronary interventions. An expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. Eur Heart J. 2018;39:3281-3300.
3. Johnson TW, Räber L, Di Mario C, et al. Clinical use of intracoronary imaging. Part 2:acute coronary syndromes, ambiguous coronary angiography findings, and guiding interventional decision-making:an expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. EuroIntervention. 2019;15:434-451.
QUESTION: Do you think there is enough evidence to indicate the use of intravascular imaging during percutaneous coronary interventions?
ANSWER: The appearance of intracoronary angiography was a major breakthrough for the management of ischemic heart disease. However, the limitations of this imaging modality became evident right from the start. The arrival of intravascular ultrasound (IVUS) 30 years ago now and then the optical coherence tomography (OCT) brought significant advances regarding diagnosis and percutaneous coronary intervention. Although the independent studied that compared IVUS and angiography showed variable results, several meta-analyses1 reinforce the use of the former. On the other hand, although the OCT is much newer compared to the IVUS and there is less scientific evidence supporting it, the excellent quality of its images has turned it into the imaging modality of choice for the management of complex plaques, the detection of complications during the procedure, and the assessment of stent implantation both in the clinical practice and clinical studies.
Q.: Which are the anatomical or clinical contexts with more evidence available?
A.: Both imaging modalities have proven their best cost-effectiveness ratio for the management of complex lesions. In this context, both provide very valuable information in calcified lesions. However, each of them has a specific profile with important differences between the 2.
The left main coronary artery disease is the location where the IVUS has proven most beneficial because it can guide the procedure, but also in long lesions and chronic total occlusions. On the other hand, the effectiveness of IVUS in patients with conditions like diabetes or acute coronary syndrome has been confirmed in former studies.
The excellent quality of the images provided by the OCT makes it very attractive especially in 3 scenarios. In the first place, in cases of acute coronary syndrome where the angiography can show non clearly culprit stenoses, the OCT can detect the presence of dissections, eroded or ruptured plaques, small thrombi or vessel wall hematomas. The second scenario is in-stent restenosis, where it can identify underlying mechanisms like underexpansion, hyperplasia and neoatherosclerosis. Finally, it is the imaging modality of choice to study stent endothelization, a very important aspect if it can be relevant enough as to decide on the continuity or not of antiplatelet therapy and, above all, in the context of clinical studies
Q.: Is the IVUS and OCT level of evidence the same?
A.: To this day, and partly due to the fact that IVUS has been with us much longer, its scientific evidence is more solid since the OCT has less often been compared to the angiography and only to IVUS in a clinical trial.2 As a consequence, the clinical practice guidelines3 show the current scientific evidence available in the following recommendations and levels of evidence:
-
– IVUS in selected cases to optimize stent implantation: IIa B.
-
– IVUS to determine severity and optimize stent implantation in unprotected left main coronary artery disease: IIa B.
-
– IVUS or OCT to study the underlying mechanism of stent failure: IIa C.
-
– OCT in selected cases to optimize stent implantation: IIb C.
Q.: What are the advantages of OCT with respect to IVUS during percutaneous coronary interventions?
A.: Although the IVUS has 10 times less resolution than the OCT and, therefore, worse image quality, it is superior to the OCT in some aspects. The IVUS has a greater capacity to penetrate soft tissues (5-6 mm vs 1-2 mm of the OCT) and detects the total thickness of the vessel, which is an advantage when having to decide on the diameter of the stent in relation to the size of the vessel. Its second greatest advantage is that it does not require washing the artery to eliminate the red blood cells that complicate the performance of an OCT so much. Finally, in certain patients, especially those with left main coronary artery disease, and since no artery washing is required, both scientific evidence and image quality make IVUS the imaging modality of choice.
Q.: Which cases would be eligible for using IVUS and which for using OCT?
A.: The characteristics of the patient and the lesion condition the use of 1 imaging modality over the other. For example, IVUS is more adequate in cases of:
-
– Left main coronary artery disease, especially proximal: IVUS is supported by more scientific evidence as shown by the guidelines. On the other hand, in many cases, the arterial washout with contrast cannot be performed properly, which leads to suboptimal image quality with the OCT.
-
– Aorto-ostial junction, both in the left and right coronary arteries since, as we already mentioned, the OCT does not provide a proper image quality.
-
– Kidney disease or patients in whom the amount of contrast should to be limited: although a few alternatives to this have been described like the use of dextran to induce less kidney damage, in general, all these agents cause volume overload which is ill-advised in complex procedures. It is estimated that the use of OCT involves some extra 17 mL and 70 mL of contrast per case.
In the remaining scenarios, the superior image quality provided by the OCT is a very significant advantage, which means that it is the imaging modality of choice when the aforementioned situations don’t take place.
There is a subgroup of lesions where the OCT has become very popular. I am talking about bifurcations that amount to 15% of all the percutaneous coronary interventions performed these days. The use of intravascular imaging is highly recommended here since they are lesions with an associated higher rate of thrombosis and restenosis. Besides, the latter is difficult to treat, and a top level of excellence is advised in the results obtained that can be optimized with the use of imaging modalities, especially OCT. Having said this, we should always remember the limitation imposed by the use of additional contrast at the end of a complex case. Therfore, despite the fact that the image quality of IVUS is worse compared to OCT, at times it can replace it. The recent advances made in the design of new higher-resolution IVUS catheters can be an alternative to bear in mind when the use of OCT is somehow problematic.
Q.: What studies are necessary to establish the role of these imaging modalities during percutaneous coronary interventions?
A.: Since the left main coronary artery is the location where IVUS performs better and taking into consideration the current class IIa recommendation with grade B level of evidence, it would be very interesting to have studies available that would enable an upgrade to a class I recommendation. Regarding the left main coronary artery disease, these studies can also be very interesting for another reason. For example, the EXCEL and NOBLE clinical trials are no longer producing more evidence on the percutaneous revascularization of these patients. This means that «something new» should come up if we want to show additional benefits to be able to upgrade the levels of recommendations and evidence. Examples of these trials in the pipeline are (ClinicalTrials.gov):
-
– The OPTIMAL NCT04111770 clinical trial: an international, randomized, controlled, multicenter clinical trial where 800 patients will be randomized in a 1:1 ratio to undergo IVUS or angiography-guided percutaneous revascularization. Patients will be followed for 2 years after the index procedure.
-
– The INFINITE NCT04072003: a study with a similar design to the previous one with 616 patients with left main coronary artery disease with bifurcation types 1.1.1 or 0.1.1 according to the Medina classification. In the angiography group, patients will be treated with 2 stents and the implantation technique will be left to the operator’s criterion. However, in the IVUS group the lateral branch will be treated based on the lumen area as seen on the IVUS (in cases with lumen areas > 4 mm2 no stent will be implanted).
On the other hand, the situation with the OCT is different. This imaging modality has grown rapidly thanks to its excellent image quality. However, scientific support is not as strong. Added to the studies where this imaging modality is not the study primary endpoint but the tool to show the primary endpoint in subgroups of patients (acute coronary syndrome with or without ST-segment elevation and studies focused on the results of certain stents), it would be interesting to conduct clinical trials on the OCT. These studies primary endpoint would be to improve clinical results to increase the level of recommendation published by the guidelines. An example of this type of studies is the ILUMIEN IV: OPTIMAL PCI NCT03507777 where 3656 patients will be randomized in a 1:1 ratio to compare the result of angiography vs OCT-guided stenting at a 2-year follow-up.
Q.: What technical advances are available today or could be available in the near future regarding the OCT?
A.: Over the last few years, the following advances have been made regarding IVUS, some of them are still in the pipeline.
-
– High-definition IVUS: of up to 60 MHz and a superior image quality compared to the 20 MHz or 40 MHz IVUS. It is already available for clinical use.
-
– IVUS-angiography co-registration: this system integrates the information provided by the IVUS and the angiography in such a way that it can locate the artery of each spot analyzed by the IVUS. It is also available for clinical use.
-
– Dual-element IVUS transducer: one 35 MHz transducer to generate standard IVUS images plus another 70 MHz transducer to receive the second harmonic signals induced by the 35 MHz ultrasound. This dual transducer performs simultaneous analyses of the general anatomy through 35 MHz images and the media and adventitia layers through harmonic signals. It is still in the preclinical phase.
-
– Hybrid IVUS and OCT single transducer: undoubtedly this is the most advanced project of all by far, and it can acquire IVUS, OCT or OCT-IVUS images of the same spot with high sensitivity (up to 50 MHz for the IVUS). It is also in the preclinical phase.
REFERENCES
1. Buccheri S, Franchina G, Romano S, et al. Clinical Outcomes Following Intravascular Imaging-Guided Versus Coronary Angiography-Guided Percutaneous Coronary Intervention With Stent Implantation:A Systematic Review and Bayesian Network Meta-Analysis of 31 Studies and 17,882 Patients. JACC Cardiovasc Interv. 2017;10:2488-2498.
2. Ali ZA, Maehara A, Genereux P, et al. Optical coherence tomography compared with intravascular ultrasound and with angiography to guide coronary stent implantation (ILUMIEN III:OPTIMIZE PCI):a randomised controlled trial. Lancet. 2016;388:2618-2628.
3. Neumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019;40:87-165.
QUESTION: After the IABP-SHOCK II clinical trial, which would you say is the utility of the intra-aortic balloon pump (IABP)?
ANSWER: The IABP-SHOCK II1 did not show any benefits in the 30-day mortality rate or major complications rate when the IABP was compared to conventional therapy in patients with post-infarction cardiogenic shock undergoing primary percutaneous coronary intervention (PCI). No differences were found either in the mortality rate or quality of life of survivors in the studies conducted at 12-month2 and 6 year-follow-up.3
European guidelines4 downgraded the systematic use of IABP to a class IIIb level of evidence leaving the indication IIa for the management of infarct related mechanical complications. This decreased the use of IABP in the routine clinical practice. However, it is still used in critical care units because it is easy to use, can be implanted quickly, and is cheaper compared to other devices.
Taking into account the limitations of these studies and although we do not use it systematically in our center like we used to years ago, we still implant it as the first-line strategy for the management of infarct related mechanical complications. Also, in patients with extensive acute myocardial infarction (IAM) and hemodynamic instability because it improves coronary perfusion and increases the cardiac output.
Q.: In the congress held by the American Heart Association back in 2019 several observational registries showed more adverse events and higher costs compared with the use of the Impella device compared to the IABP. However, these results may be due to the effect of multiple biases. What do you think of all this?
A.: These observational registries revealed a higher rate of adverse events, and higher costs associated with the use of the Impella device compared to the IABP. However, they have some limitations: they mixed different types of Impella devices (2.5, CP, and 5) and different etiologies of cardiogenic shock. Also, in most of the patients the device was implanted after the primary percutaneous coronary intervention. In one of these registries that would later be published in Circulation,5 patients implanted electively with the Impella device in the cardiogenic shock setting were also included.
We have been getting more and more data that the management of cardiogenic shock through the creation of specialized units, invasive hemodynamic monitorization, and implantation of the Impella CP device prior to the PCI improves the results of revascularization and reduces the size of the infarction and the 30-day mortality rate in patients with post-infarction cardiogenic shock. Some studies like the Detroit shock initiative6 and the national cardiogenic shock initiative7 have already discussed this theory.
Currently, several randomized clinical trials are trying to come to terms with this hypothesis: the Danger shock trial8 (support with Impella CP prior to the PCI vs conventional therapy in the management of post-infarction cardiogenic shock), the RECOVER IV (Impella before PCI vs PCI without Impella in the management of infarction related cardiogenic shock), and the STEMI DTU (ClinicalTRials.gov NCT03947619) (Impella CP and PCI delayed 30 min. vs immediate PCI in patients with ST-segment elevation acute myocardial infarction of anterior location without shock). The latter is based on the results from a pilot study on safety and feasibility. The DTU-STEMI pilot trial9 proved that it is safe and feasible to perform a PCI 30 min. after LV (left ventricular) unloading with the Impella CP device in patients with anterior AMI without shock.
Regarding high-risk PCIs, the PROTECT-II trial10 that randomized 452 patients who underwent high-risk PCIs with IABP or Impella 2.5 support showed no differences in the cardiovascular events occurred at the 30- and 90-day follow-up. However, fewer adverse events were seen at the 90-day follow-up in the Impella 2.5 group.
The PROTECT IV study is underway (Impella as support for high-risk PCI vs PCI without hemodynamic support). It will start in 2021 and it will be part of the clinical evidence for the class I recommendation for the Impella device in high-risk PCIs.
The results of the studies currently underway are promising because I think it is LV unloading prior to the PCI that will certainly improve the mortality of post-infarction cardiogenic shock. To this day and until proven wrong, I strongly believe that the Impella CP implanted prior to the PCI is the device of choice for the management of post-infarction cardiogenic shock.
Until we have more data available, I think high-risk PCIs should be handled individually based on the characteristics of the patients and the experience of the heart teams with these devices and in the management of complex PCIs.
Q.: Is your center savvy in the use of extracorporeal membrane oxygenation (ECMO)? What evidence exists for its use in the management of cardiogenic shock in patients with infarction? What studies would be needed in this context to consolidate its indication?
A.: Some of the advantages of the ECMO device are that it is easy to use and can be implanted quickly. Its main hemodynamic effect is an increased mean arterial blood pressure that is higher compared to other devices. However, this advantage is precisely the cause for its most important limitation: the problem of LV unloading in relation to an increased afterload. This increases myocardial oxygen demand and produces deleterious effects on the size of the infarction and its potential recovery. From the pathophysiological point of view, it is not a good device for the management of post-infarction cardiogenic shock.11 Its basic role rests in its hemodynamic effect and improved organ perfusion; that is, it is indicated for patients in INTERMACS 1 situation. To overcome the limitation of inadequate LV unloading, the best option is to add an Impella device that is capable of producing the most powerful hemodynamic effect for LV unloading in ECMO.12
Our center is highly experienced in the use of ECMO for the management of cardiogenic shock of any known etiology. We use it for the management of patients with post-infarction deep cardiogenic shock (INTERMACS 1) in the coronary care unit before or after the primary percutaneous coronary intervention. In these patients we initially implant the IABP to improve LV unloading. If the balloon is insufficient, the next step is to add an Impella device.
There are no randomized studies available on the use of ECMO for the management of post-infarction cardiogenic shock. We’ll have to wait for the results from other devices. If the hypotheses formulated prove right, ECMO will play a significant role in the management of patients with AMI in whom the Impella device is insufficient or in hospitalized patients with hemodynamic compromise used in combination with the Impella device to overcome the limitation of inadequate ventricular unloading.
Q.: What escalation of mechanical circulatory support do you recommend in hemodynamically compromised patients or patients with post-infarction shock?
A.: I think the first thing to do is to include cardiogenic shock in specialized units experienced in the management of these patients and use of this type of devices. The right selection of patients, invasive hemodynamic monitorization, and use of inotropes for stabilization purposes is of paramount importance until early device implantation.
With the current data and taking into account the costs of the different devices and the complications associated there are different considerations to be made when choosing one device over the other:
–Patients with extensive infarction and pre-shock, mechanical complications or ventricular arrhythmias: IABP.
–Patients without deep shock (INTERMACS 2): Impella CP prior to the percutaneous coronary intervention and, if not enough support is achieved, add ECMO.
–Patients in deep shock (INTERMACS 1): ECMO combined with balloon or Impella device if there are problems unloading the left ventricle.
CONFLICTS OF INTEREST
None reported.
Corresponding author: Unidad de Cardiología-Críticos, Pabellón 17-1, Hospital Universitario Marqués de Valdecilla, Avda. Valdecilla s/n, 39008 Santander, Cantabria, Spain. E-mail address: (V. Burgos Palacios).
REFERENCES
1. Thiele, H, Zeymer, U, Neumann, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med. 2012;367:1287-1296.
2. Thiele, H, Zeymer, U, Neumann, et al. Intraaortic Balloon Pump in cardiogenic shock II (IABP-SHOCK II) trial investigators. Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II):final 12 month results of a randomised, open-label trial. Lancet. 2013;382:1638-1645.
3. Thiele H, Zeymer U, Thelemann N, et al. Intraaortic Balloon Pump in Cardiogenic Shock Complicating Acute Myocardial Infarction:Long-Term 6-Year Outcome of the Randomized IABP-SHOCK II Trial. Circulation. 2019;139:395-403.
4. Ibanez, B, James, S, Agewall, S, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation:the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39:119-177.
5. Amin AP, Spertus JA, Curtis JP, et al. The Evolving Landscape of Impella Use in the United States Among Patients Undergoing Percutaneous Coronary Intervention With Mechanical Circulatory Support. Circulation. 2020;141:273-284.
6. Basir MB, Schreiber T, Dixon S, et al. Feasibility of early mechanical circulatory support in acute myocardial infarction complicated by cardiogenic shock:The Detroit cardiogenic shock initiative. Catheter Cardiovasc Interv. 2018;91:454-461.
7. Basir MB, Kapur NK, Patel K, et al. Improved Outcomes Associated with the use of Shock Protocols:Updates from the National Cardiogenic Shock Initiative. Catheter Cardiovasc Interv. 2019;93:1173-1183.
8. Udesen NJ, Møller JE, Lindholm MG, et al. Rationale and design of DanGer shock:Danish-German cardiogenic shock trial. Am Heart J. 2019;214:60-68.
9. Kapur NK, Alkhouli MA, DeMartini TJ, et al. Unloading the Left Ventricle Before Reperfusion in Patients With Anterior ST-Segment-Elevation Myocardial Infarction. A pilot study using the impella CP. Circulation. 2019;139:337-346.
10. O'Neill WW, Kleiman NS, Moses J. A prospective, randomized clinical trial of hemodynamic support with Impella 2.5 versus intra-aortic balloon pump in patients undergoing high-risk percutaneous coronary intervention:the PROTECT II study. Circulation. 2012;126:1717-1727.
11. Rihal CS, Naidu SS, Givertz MM, et al. 2015 SCAI/ACC/HFSA/STS clinical expert consensus statement on the use of percutaneous mechanical circulatory support devices in cardiovascular care. J Am Coll Cardiol. 2015;65:e7-e26.
12. Donker DW, Brodie D, Henriques JPS, BrooméM. Left ventricular unloading during veno-arterial ECMO:a review of percutaneous and surgical unloading interventions. Perfusion. 2019;34:98-105.
- Debate: Mechanical circulatory support in relation to coronary intervention. The interventional cardiologist perspective
- Debate: Angiography-derived FFR. The pressure guidewire perspective
- Debate: Angiography-derived FFR. The angiographic perspective
- Debate: Closure of patent foramen ovale. The interventional cardiologist perspective
Original articles
Review Articles
Original articles
Editorials
Ventricular pressure-volume loop and other heart function metrics can elucidate etiology of failure of TAVI and interventions
aDepartment of Mechanical Engineering, McMaster University, Hamilton, Ontario, Canada
bSchool of Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada
Special articles
Role of computed tomography in transcatheter coronary and structural heart disease interventions
aServicio de Cardiología, Hospital Universitario Álvaro Cunqueiro, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Vigo, Pontevedra, Spain
bServicio de Cardiología, Hospital de la Santa Creu i Sant Pau, Instituto de Investigación Biomédica Sant Pau (IBB Sant Pau), Barcelona, Spain
cServicio de Cardiología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain
dCentro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Spain
Debate
“Orbiting” around the management of stable angina
The interventional cardiologist’s perspective
aServicio de Cardiología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain
bCentro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Spain
The clinician’s perspective
aInstituto Cardiovascular, Hospital Clínico San Carlos, Madrid, Spain
bDepartamento de Medicina, Facultad de Medicina, Universidad Complutense, Madrid, Spain