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
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Debate: MitraClip. The interventional cardiologist perspective
QUESTION: What is the prevalence of bicuspid aortic valve (BAV) in your case series of transcatheter aortic valve implantation (TAVI) to this date? And what’s the patients’ surgical risk?
ANSWER: Over 1000 TAVIs have already been performed at our center, and the prevalence of BAV stands at around 4.4%. It is greater compared to the Spanish TAVI registry where nearly 2% of the patients treated with TAVI have BAV.1 Thanks to the use of computed tomography scan as a systematic imaging modality to plan TAVI, its diagnosis has gone up. As a matter of fact, our group included the number of patients treated with TAVI or surgery in 2019 in 17 Spanish centers being the prevalence of BAV around 4.6%, and 16%, respectively. At times, the diagnosis of BAV is not an easy one, and when the heart valve is highly unstructured and calcified, it can go unnoticed. Therefore, it can be underdiagnosed in our series of TAVI. However, an «active» search can increase the number of diagnoses.
In our series the risk profile of these patients is intermediate-high. The mean age is 80 years old with a similar distribution by sex. The risk scores measured were the logistic EuroSCORE (14.8%), the EuroSCORE II (5.8%), and the STS (5.7%). However, these scores are influenced by the ones obtained in younger patients (< 75 years) that, although with lower scores, have proven inoperable or are very high-risk surgical patients (mainly due to a respiratory condition or hemodynamic instability).
Q.: What evidence do we have for TAVI to treat bicuspid aortic valve stenosis? Are the actual results equivalent to the ones reported for the non-bicuspid aortic valve?
A.: In short, I would say that although scarce (mainly from retrospective registries), evidence is mounting. The results coming from the oldest series were worse. However, they are currently similar with certain differences.
The evidence available on TAVI in the BAV aortic stenosis fall into 3 categories: a) TAVI in the BAV vs TAVI in the tricuspid valve; b) different types of TAVI in the BAV (TAVI vs TAVI), and c) TAVI vs surgery in the BAV.
The early studies showed that TAVI performed in the BAV had higher rates of paravalvular leak, embolization, need for second valve implantation, and a lower rate of successful device implantation. Thanks to the technical advances made and second and third-generation valves, these results have equalized. However, there is still a significant rate of stroke (2.5%) that is even higher compared to tricuspid valves.2 A meta-analysis demonstrated that the rate of paravalvular leak is still a little higher in self-expanding valves, as well as the rate of mechanical complications in balloon-expandable valves.3 No all valves are the same for the different anatomical and clinical settings. In the BAV only 1 retrospective registry has been published comparing the Edwards SAPIEN 3 valve (Edwards Lifesciences LLC, United States) to the Evolut R/Pro (Medtronic, United States). The outcomes were similar regarding mortality and stroke, but with higher rates of paravalvular leak and device embolization, and fewer overall events of successful implantation in the self-expanding valve group vs higher gradients (approximately 2 mmHg) in the balloon-expandable valve group.4 In the most recent series published on the SAPIEN 3 valve in the context of the Partner-3 trial, a group of patients with BAV was compared—after propensity score-based risk adjustment—to another group of patients with tricuspid valve. It turned out that the clinical outcomes overlapped in both (mortality and stroke rates of 0% and 1.4%, respectively at 30 days). We should mention that the CoreValve Evolut device achieved an indication in patients with BAV (based on the TVT registry5) while the SAPIEN 3 valve does not have a specific contraindication in this context in its instructions for use. However, the remaining valves available today are specifically contraindicated for BAV in the instructions for use. Finally, the outcomes of TAVI vs surgery in the BAV were published in 2 studies, one with in-hospital outcomes and the other with the outcomes reported at the 2-year median follow-up.6,7 Patients treated with TAVI had a higher rate of pacemaker implantation, and better data regarding bleeding, vascular complications, and lengths of stay with similar rates of in-hospital mortality and stroke at the 2-year follow-up. Therefore, although we still don’t have robust evidence that TAVI is superior to surgery regarding the BAV, there is no single piece of evidence that says that TAVI fares worse compared to surgery.
Q.: What special considerations should be made with TAVI when performed on the bicuspid aortic valve? Are there any anatomical variants with specific technical implications?
A.: The first consideration should be to know whether we are really talking about a BAV or not. Like I said, in heavily calcified and unstructured valves it can go unnoticed. For procedural planning purposes, it is essential to make a thorough assessment of the baseline computed tomography scan. It should provide us with detailed information on the valve and the ascending aorta to obtain optimal results. In the first place, we should know both the type of BAV (type 0, I or II) and its morphology. In highly asymmetrical type 0 valves with a heavily calcified raphe, the expansion of the valve can be inadequate (very elliptical) and affect the hemodynamic outcomes (due to gradients and paravalvular regurgitation). Also, both the location of the raphe and calcification per se can have an impact on the position of the valve that can move towards either one of the sinuses (with greater risk of coronary obstruction in case of displacement towards the left or the right sinus). We should mention that the presence of a calcified raphe plus excessive leaflet calcification has been associated with a higher mortality rate.8 The computed tomography scan can also be used to measure the right size of the valve both at annular and supra-annular level (intercommissural distance) always remembering that minimal valve oversizing is often necessary.
Once the right procedural planning is in place, the technical considerations on the day of the surgery should be:
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–Avoid brain damage as much as possible and, if possible, always use cerebral protection devices.
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–Use high support guidewires like Lunderquist (Cook Medical, United States) or Back-up Meier (Boston Scientific, United States) when treating tortuous aortas.
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–Use the necessary time to locate the angiographic plane for implantation since it is often more complex compared to tricuspid valve cases.
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–Always predilate (in most cases with the minimum diameter and without exceeding the medium) and watch the degree of balloon opening and calcium displacements from the leaflets towards the coronary arteries. The strategy of performing a simultaneous injection during predilation provides us with valuable information to analyze the risk of coronary occlusion and select the size of the valve.
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–Select the right type of TAVI based on the patient’s characteristics. Self-expanding valves with less radial strength can remain underexpanded so before their implantation we should always acquire several projections to confirm their correct expansion. If there is a high risk of rupture in the annulus with an aggressive expansion, the Evolut Pro+ valve can be used. However, if the risk of aortic regurgitation is high, the SAPIEN 3 Ultra valve should rather be used. We should mention that these risks happen together and the trade-off is complex. The tortuosity of the aortic arch and the horizontally of the ascending aorta (very common in the BAV) can also help us select a flexible valve or with a deflectable catheter. Another significant aspect to select the type of valve is the operator’s experience.
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–If postdilation is required (needed in over 50% of the cases with self-expanding valves), the balance between the rupture of the annulus and the leak should be observed when selecting the balloon size. On many occasions, the annuli of BAVs are large meaning that large balloons will also be needed (26 mm, 28 mm or 30 mm). Still, balloons this big are not always available at the cath lab.
Q.: Which cases with BAV do you think are clearly eligible for TAVI and which are not?
A.: This is a very relevant question because, like I said, evidence is scarce and barely any randomized trials have been published on this regard (at least in the short and mid-term) comparing TAVI to surgery in the BAV setting. Therefore, decisions should be made based on the operator’s experience and the local outcomes. When examining a patient with BAV for TAVI a series of clinical, and anatomical (or technical) aspects should be taken into consideration. The clinical features in favor of TAVI are the same as for tricuspid valves, that is, old, frail, and female patients (> 75 years) with comorbidities and lack of coronary artery disease or other concomitant valvular heart disease. The favorable anatomical aspects would be a suitable femoral access, type 1 bicuspid anatomy (versus type 0 and 2), small annuli, mild or moderate calcification, no dilatation of the ascending aorta, no calcification of the raphe, and no risk of coronary artery occlusion. I would use TAVI as the first-line therapy for high-risk frail or elderly patients. However, I would use surgery for young low-risk patients (< 70 years). It should be the job of the heart team to know how to deal with intermediate settings in each case like young patients with comorbidities and intermediate risk but with a favorable anatomy for TAVI or high-risk older patients with an unfavorable anatomy for TAVI. Something that should be studied based on the patients’ clinical and anatomical features is whether the long-term results of surgery are predominant compared to its immediate risks or if, on the contrary, TAVI less invasive approach is preferred in this balance even after obtaining suboptimal outcomes in highly unfavorable anatomies. Thanks to the technical advances made, the new valves available, and the experience gained with TAVI with careful procedural planning good results can be achieved even in complex settings. However, since a proportion of patients with BAV are young, we interventional cardiologists need to be aware of the heterogeneity of this disease, refine the technical details of implantation, and the selection of patients and devices to optimize results.
FUNDING
None reported
CONFLICTS OF INTEREST
L. Nombela-Franco has received a research grant (INT19/00040) from the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III), is a proctor for Abbott, and has received speaking fees from Edwards Lifesciences, and Boston Scientific.
REFERENCES
1. Jiménez-Quevedo P, Nombela-Franco L, Muñoz-García E, et al. Early clinical outcomes after transaxillary versus transfemoral TAVI. Data from the Spanish TAVI registry. Rev Esp Cardiol. 2021. https://doi.org/10.1016/j.rec.2021.07.019.
2. Makkar R, Yoon SH, Leon MB, et al. Association Between Transcatheter Aortic Valve Replacement for Bicuspid vs Tricuspid Aortic Stenosis and Mortality or Stroke. JAMA. 2019;321:2193-2202.
3. Montalto C, Sticchi A, Crimi G, et al. Outcomes After Transcatheter Aortic Valve Replacement in Bicuspid Versus Tricuspid Anatomy:A Systematic Review and Meta-Analysis. JACC Cardiovasc Interv. 2021;14:2144-2155.
4. Mangieri A, TchetchèD, Kim WK, et al. Balloon Versus Self-Expandable Valve for the Treatment of Bicuspid Aortic Valve Stenosis:Insights From the BEAT International Collaborative Registry. Circ Cardiovasc Interv. 2020;13:e00∊.
5. Forrest JK, Kaple RK, Ramlawi B, et al. Transcatheter Aortic Valve Replacement in Bicuspid Versus Tricuspid Aortic Valves From the STS/ACC TVT Registry. JACC Cardiovasc Interv. 2020;13:1749-1759.
6. Yoon SH, Kim WK, Dhoble A, et al. Bicuspid Aortic Valve Morphology and Outcomes After Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. 2020;76:1018-1030.
7. Elbadawi A, Saad M, Elgendy IY, et al. Temporal Trends and Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement for Bicuspid Aortic Valve Stenosis. JACC Cardiovasc Interv. 2019;12:1811-1822.
8. Mentias A, Sarrazin MV, Desai MY, et al. Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Bicuspid Aortic Valve Stenosis. J Am Coll Cardiol. 2020;75:2518-2519.
QUESTION: What is the prevalence of bicuspid aortic valve in the population currently eligible for surgical aortic valve replacement?
ANSWER: The prevalence of bicuspid aortic valve is around 1% to 2% of the population. Somewhere between 27% and 35% of the population will eventually require surgery at the 20-year follow-up.1 On the other hand, the associated dilatation of the ascending aorta, with conflicting results regarding its prevalence, stands at around 50% to 80%.1 At our center, 30% of all aortic valve replacements or repairs—with or without replacement of the ascending aorta—are performed on the bicuspid aortic valve. Also, this is a group of predominantly male patients with a mean age of 55 years, and different clinical features compared to the aortic stenosis described in elderly patients. Many of these patients are repaired when regurgitation is predominant with excellent clinical outcomes.
Q.: What special considerations should be made with surgery when performed on the bicuspid aortic valve?
A.: There are 3 special considerations that should be observed. In the first place, this condition affects a group of younger patients. Also, these valves have severe calcification posing great technical difficulties regarding decalcification for correct implantation under direct vison. On many occasions, eventually, the ascending aorta needs to be replaced. According to the clinical practice guidelines from the European medical societies on cardiology and thoracic surgery, the ascending aorta needs to be replaced if it is longer than 45 mm in the presence of associated valve replacement. The indication for isolated aneurysm without valvular lesion is 50 mm in the presence of associated risk factors (arterial hypertension, past medical history of dissection or aortic syndrome).2
Q.: Do you think that severe aortic stenosis in the bicuspid aortic valve is an indication for surgery per se regardless of the surgical risk?
A.: I do for the reasons I already gave you on the special characteristics of this condition that, in most cases, require surgery. The main reason is that it affects younger patients in whom other therapeutic options have not been validate with 10+year follow-ups. Other less important reasons are severe calcification, repair possibilities in the presence of double valvular lesion, and quite often, the need to replace the ascending aorta.
Q.: In your opinion, which are the cases of severe bicuspid aortic stenosis clearly eligible for surgery and which are ineligible?
A.: In principle, preferably, all cases should be treated surgically. Other options can be considered only in patients in whom surgery is contraindicated, although the evidence available on this matter is still weak. Studies on transcatheter aortic valve implantation include elderly patients with aortic stenosis. According to the European clinical practice guidelines, patients over 75 with comorbidities can be treated percutaneously. However, the severe associated calcification, and lack of scientific evidence should always be taken into consideration.3
FUNDING
None.
CONFLICTS OF INTEREST
None whatsoever.
REFERENCES
1. Detaint D, Michelena HI, Nkomo VT, Vahanian A, Jondeau G, Sarano ME. Aortic dilatation patterns and rates in adults with bicuspid aortic valves:a comparative study with Marfan syndrome and degenerative aortopathy. Heart. 2014;100:126-134.
2. Erbel R, Aboyans V, Boileau C, et al. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases:Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). ESC Committee for Practice Guidelines. Eur Heart J. 2014;35:2873-2926.
3. Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. ESC/EACTS Scientific Document Group;ESC Scientific Document Group. Eur Heart J. 2022;43:561–632.
QUESTION: Could tell us what the prevalence of angina without obstructive coronary artery disease is in patients referred for invasive angiography and how has it evolved over the last few years?
ANSWER: Nearly half of the patients referred for cardiac catheterization due to suspected stable angina have coronary arteries without obstructive lesions.1 These numbers are even higher in the series of patients studied through cardiac computed tomography to the point that up to 3 out of 4 patients do not show any obstructive lesions. Women have a higher prevalence compared to men of up to 70%. Therefore, angina without obstructive lesions should not be considered a secondary problem, but a fundamental aspect of our routine clinical practice at the cath lab. Also, these patients have high rates of recurring angina and disability,2 which means that achieving the proper diagnosis and administering the right treatment is of paramount importance.
Q.: We have been using the expression «without obstructive coronary artery disease», but it can be put into context. Shouldn’t we rather say «without angiographically significant stenoses». Do you think that the physiological significance of stenoses with guidewire pressure should always be excluded, even the mild ones?
A.: With the evidence available, I believe that the systematic use of guidewire pressures to assess mild epicardial lesions is not justified. As a matter of fact, the correlation and concordance between angiography and fractional flow reserve (FFR) are modest, which is especially important in 50% to 90% stenoses where the angiography often overestimates functional severity systematically with rates of false positives > 50%.3 On the other side of the spectrum, stenotic lesions < 50% on the angiography have a relatively low risk of being ischemic on the FFR and are almost anecdotal if < 30%. In a study conducted with 139 patients with angina and without obstructive lesions, the frequency rate of lesions with FFR ≤ 0.8 was 5%.4 On the other hand, we should mention that the cut-off value validated to tag a coronary lesion as ischemic is 0.75 although, in practice, 0.8 is used to decide on whether to revascularize or not.
Regarding the clinical benefit of this approach, the large clinical trials that have proven the utility of FFR have only studied lesions > 50%, which is why we don’t have data supporting the clinical utility of assessing mild lesions.5,6 The RIPCORD-2 trial7 presented in the Congress held by the European Society of Cardiology back in September 2021 included patients with, at least, 1 stenotic lesion > 30%. All these patients’ vessels were studied using the FFR and no clinical benefit was found. What this means is that probably the greatest benefit of FFR is to avoid unnecessary revascularizations, and to clarify the significance of truly suspicious lesions.
In practice, I think that the best thing to do is to individualize the decision-making process considering the angiographic severity, location of the lesion, and quality of angiographic assessment. A 20% lesion in a diagonal branch and a 40% lesion in the proximal left anterior descending coronary artery are 2 completely different things. Also, a focal lesion in a well-studied segment does not cast the same doubts as a long and calcified disease where a good angiographic assessment is not an easy thing to do due to curves, shortening, etc. Finally, we should remember that if a decision is made to measure microvascular function using a flow-pressure guidewire, the FFR can be established, almost at the same time, on suspicious lesions.
Q.: Once the significant stenosis of the epicardial vessel has been excluded, what should be the assessment protocol inside the cath lab?
A.: The invasive assessment of ischemia without obstructive lesions rests on 2 pillars mainly: the study of microcirculation, and the study of vascular reactivity.
The study of microcirculation consists of assessing coronary flow at rest and during maximum hyperemia. To this end, pressure and flow guidewires, whether thermodilution-based (PressureWire, Abbott, United States) or Doppler-based (Combowire, Philips, The Netherlands) are used. Baselines measures are taken, then maximum hyperemia is induced with adenosine to eventually take the same measures once again. This allows us to estimate the coronary flow reserve that is the ratio between hyperemic and baseline flow (which should be > 2). Coronary flow reserve < 2 means that, in situations of exercise or other stressors, the patient cannot duplicate his oxygen supply to the myocardium eventually, thus leading to ischemia easily. Added to flow coronary reserve, the combination of pressure and hyperemic flow, can also estimate microvascular resistance. The most widely used measure is the microvascular resistance index (considered pathological if > 25.)8
The second part is to assess vasoreactivity since coronary arteries do not necessarily respond to physiological stimuli the same way they do to adenosine. As a matter of fact, coronary flow and vascular tone both of epicardial artery and microcirculation largely depend on the production of nitric oxide by the endothelium. If this production does not properly work, paradoxical vasoconstriction can be seen in physiological situations that would require hyperemia. That is why it is important to assess coronary reactivity, preferably using the acetylcholine provocation testing. It allows us to discard the presence of vasospastic angina, and endothelial dysfunction. We have recently published an article on REC: Interventional Cardiology with a detailed description on how to run and then interpret an acetylcholine provocation testing.9
This approach based on microvascular function and on the acetylcholine provocation testing has been backed by a group of experts from the European Society of Cardiology.8 Regarding the logistics of the procedure, each lab should assess, depending on time availability, resources, and experience whether to perform the procedure ad hoc or whether to stage it, and arrange the order in which the tests will be run. We should bear in mind that, although the assessment of microcirculation requires the previous administration of nitroglycerin, the acetylcholine provocation testing requires just the opposite. Therefore, a possibility is to perform the angiography without nitroglycerin first, then the acetylcholine provocation testing, and finally measure the microvascular function. If nitroglycerin has been administered to achieve the diagnosis, the best thing to do is to measure the microvascular function next and leave the acetylcholine provocation testing for the end.
Q.: Is it possible to draw therapeutic implications from the comprehensive assessment of micro- and macrovascular coronary physiology?
A.: The main problem with microvascular and endothelial dysfunction is that no large clinical trial has ever confirmed any benefits regarding adverse events with any drugs. However, this should not take us to therapeutic nihilism because some former studies have proven the utility of different drugs reducing symptoms and improving quality of life.
If the patient is diagnosed with microvascular dysfunction, the first-line therapy here is beta-blockers. As coadjuvant or alternative therapy ivabradine, ranolazine, nicorandil, and calcium channel blockers can be used; nitroglycerin is not very useful here because it has a minor effect on microcirculation. Statins, and renin-angiotensin system inhibitors are advised too for the primary prevention of events.
If endothelial dysfunction-induced vasoconstriction or vasospastic angina are predominant, beta-blockers are ill-advised since they can make things worse. In this case, the first-line therapy is calcium channel blockers, nitrates, and nicorandil. The use of statins, and renin-angiotensin system inhibitors can be considered here too.
Empirical treatment has often been advised as an easier approach compared to physiological diagnosis and targeted therapy. Once again, each center should adapt its own clinical practice to its own possibilities. However, my own experience is that when these patients are not properly studied, they are not committed to the frequent visits that a careful empirical treatment would require; on the contrary, they are often discharged from the hospital and assessed at the 1-year follow-up, preventing us from conducting a proper follow-up of the symptoms and the effectiveness of treatment. On the other hand, considering that based on the physiological problem, there are very little effective treatments (like nitrates in microvascular dysfunction), and others are harmful (like beta-blockers in vasospasm), I think empirical treatment confront us with true dilemmas when treating patients who are not doing well.
Q.: What is the clinical evidence behind the invasive comprehensive assessment of coronary circulation? Have some advantages been identified regarding prognosis?
A.: Numerous studies from the 90s have proven that physiological disorders in patients with angina and without obstructive lesions are directly associated with myocardial ischemia and with long-term prognosis, as well as with the presence of atheromatous plaques and vulnerability data from intravascular imaging modalities. This is important because it is wrong to assume that all patients with angina and without lesions have the same disease and the same benign prognosis. Truth is that patients with endothelial and microvascular dysfunction have a far worse prognosis compared to patients with normal studies. Also, small trials have allowed us to establish the efficacy of different drugs based on the type of physiological dysfunction, as we have already discussed, thus supporting targeted therapy.
Regarding the prognostic benefit of individualized therapy, the CorMicA trial proved that this approach is superior to empirical treatment offering a better quality of life after 6 and 12 months.10 To this date, we are still lacking studies with large enough samples to detect benefits regarding the adverse events. The iCorMicA trial (clinicaltrials.gov. Identifier: NCT04674449), currently ongoing, will be recruiting 1500 patients to study the benefits in quality of life and adverse events. In any case, with the results of the ISCHEMIA trial in mind,11 I believe that only focusing on reducing hard events is a mistake that can prevent patients from receiving therapies that do help from the symptomatic and functional standpoint. In conclusion, I think there are enough scientific data to say that patients with angina and without obstructive lesions benefit from knowing their physiology and receiving individualized therapies.
FUNDING
None whatsoever.
CONFLICTS OF INTEREST
The author has received payments for training sessions organized by Abbott.
REFERENCES
1. Wang ZJ, Zhang LL, Elmariah S, Han HY, Zhou YJ. Prevalence and Prognosis of Nonobstructive Coronary Artery Disease in Patients Undergoing Coronary Angiography or Coronary Computed Tomography Angiography. Mayo Clin Proc. 2017;92:329-346.
2. Shaw LJ, Merz CNB, Pepine CJ, et al. The Economic Burden of Angina in Women With Suspected Ischemic Heart Disease:Results From the National Institutes of Health-National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation. Circulation. 2006;114:894-904.
3. Park S-J, Kang S-J, Ahn J-M, et al. Visual-Functional Mismatch Between Coronary Angiography and Fractional Flow Reserve. JACC Cardiovasc Interv. 2012;5:1029-1036.
4. Lee BK, Lim HS, Fearon WF, et al. Invasive evaluation of patients with angina in the absence of obstructive coronary artery disease. Circulation. 2015;131:1054-1060.
5. Tonino PA, De Bruyne B, Pijls NH, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009;360:213-224.
6. De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367:991-1001.
7. Curzen N. RIPCORD 2:does routine pressure wire assessment influence management strategy of coronary angiography for diagnosis of chest pain?En:ESC Congress 2021. The Digital Experience;2021, 27-30 August. Available online:https://digital-congress.escardio.org/ESC-Congress/sessions/2835-hot-line-ripcord-2. Consultado 4 Sep 2021.
8. Kunadian V, Chieffo A, Camici PG, et al. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology &Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. Eur Heart J. 2020;41:3504-3520.
9. Gutiérrez E, Gomez-Lara J, Escaned J, et al. Valoración de la función endotelial y provocación de vasoespasmo coronario mediante infusión intracoronaria de acetilcolina. Documento técnico del Grupo de Trabajo de diagnóstico intracoronario de la Asociación de Cardiología Intervencionista. REC Interv Cardiol. 2021. https://doi.org/10.24875/RECIC.M21000211
10. Ford TJ, Stanley B, Sidik N, et al. 1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA). JACC Cardiovasc Interv. 2020;13:33-45.
11. 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.
QUESTION: Is there a specific profile of patients with angina and without obstructive coronary artery disease?
ANSWER: Although we have been paying more attention to angina without obstructive coronary artery disease over the last few years (a more truthful denomination compared to ischemia with normal coronary arteries because it focuses on the clinical problem and also because many patients don’t have strictly normal coronary arteries) we still don’t know much about this syndrome. Syndrome X was the term coined back in 1973 after the group of patients with normal coronary arteries that was called group X.1 Actually this term is more appropriate since this is the letter used in algebra to represent something that remains unknown.
Answering your question, it is more common in women; it is often exertional although a different kind of pattern has been reported too (first effort, at rest during certain hours, especially at night-time, exertional dyspnea); also, it is associated with known cardiovascular risk factors since most patients with angina and without obstructive coronary artery disease have coronary atherosclerosis.2 Obesity, the association with inflammatory diseases (such as systemic lupus erythematous), mood swings, intolerance to different drugs are not rare, and make us have to try several combinations to control de symptoms.
Although it seems reasonable to suspect that a patient with angina may not have coronary artery lesions justifying the symptoms, these patients’ profile is somehow similar to that of patients with clinically significant coronary artery lesions. Only an imaging modality capable of discarding clinically significant coronary artery disease can lead to a definitive diagnosis of angina without obstructive coronary artery disease.
Q.: The diagnosis of type of angina is, by definition, achieved after performing an invasive coronary angiography, but since the use of the computed tomography (CT) scan for coronary artery assessment has become more popular, can it also be diagnosed with a non-invasive angiography with a CT scan?
A.: To achieve the diagnosis of angina without obstructive coronary artery disease the following requirements need to be met:3 a) compatible symptoms, b) lack of obstructive coronary artery disease, c) myocardial ischemia, and d) microvascular dysfunction. Therefore, if microvascular dysfunction is not confirmed, the diagnosis cannot be achieved. To answer this question properly we should ask ourselves a couple more questions first: can we diagnose microvascular dysfunction with non-invasive imaging modalities including the CT scan? also, can we achieve the diagnosis only with the clinical signs and proof that there is no obstructive coronary artery disease?
The diagnosis of microvascular dysfunction with non-invasive imaging modalities is feasible, although these are expensive or have been insufficiently validated. Positron emission tomography4 and magnetic resonance imaging5 have been able to confirm the presence of microvascular dysfunction in patients without macrovascular disease in different clinical settings. Contrast echocardiography6 and Doppler echocardiography of the left anterior descending coronary artery7 have also yielded favorable results in this context, but they are barely used.
Although it does not seem right to achieve the diagnosis without prior confirmation of microvascular dysfunction, it can be reasonable under certain circumstances. If the patient has typical symptoms and cardiovascular risk factors, treatment can be initiated after discarding obstructive coronary artery disease with a CT scan. If symptoms cannot be controlled, we can turn to the invasive study of microvascular function. This can be the go-to strategy in elderly or frail patients or with severe noncardiac diseases. It can even be used for the rest of patients since delaying symptom control does not compromise or worsen prognosis.
Q.: In the presence of mild or moderate stenoses on the CT scan, do you think that a non-invasive assessment of ischemia can help?
A.: Theoretically speaking, as I have already mentioned, we need confirmation of myocardial ischemia to achieve a definitive diagnosis of microvascular disease. There are situations, however, when we can assume the diagnosis if the patient shows typical symptoms and obstructive coronary artery disease has been discarded.
In patients with CT scans showing non-severe coronary artery lesions, we need to make sure that these lesions are not functionally significant before accepting the diagnosis of microvascular disease. The milder the lesion, the more certain we’ll be that it is a non-functionally significant lesion, but microvascular dysfunction. Therefore, in moderate lesions, functional assessments are necessary to discard functionally significant disease. This assessment can be made while the CT scan is being performed by assessing coronary flow reserve8 or with functional tests to see if there are traces of ischemia, and whether these traces originate at the diseased artery.
In any case, to me this question looks more like an academic issue than a practical one. If a patient has angina pectoris, a positive functional test for ischemia, a CT scan showing moderate disease of a coronary artery, and no left main coronary artery disease, medical therapy can be initiated, and the evolution of symptoms assessed. That is so because prognosis is not much better with an invasive approach as the ISCHEMIA trial proved.9
Q.: There are times when, depending on the center, the clinician can find himself with a symptomatic patient for angina who has been diagnosed with lack of coronary stenoses without even an invasive study of coronary physiology. What would the role of non-invasive imaging modalities be here?
A.: That is correct, a few years ago that was the rule of thumb: coronary artery disease was discarded, and there was no need to assess the vascular function. Currently, cardiologists are more aware of its importance, in part due to the interest shown by interventional cardiologists in this disease. Even so, we still see patients with angina pectoris in whom obstructive epicardial vessel disease has been discarded, but endothelium-related o non-related vascular dysfunction hasn’t.
A positive ischemia assessment testing supports the diagnosis of microvascular dysfunction and, even in the absence of an invasive study of coronary physiology, it is good enough to initiate therapy. But if the patient does not get any better with the treatment suggested the invasive assessment of coronary physiology will be necessary to direct therapy towards the specific origin that’s causing the coronary disorder.
Q.: What specific medical therapies are optimal based on the profile of coronary micro- and macrovascular pathophysiology?
A.: Evidence-based recommendations are very scarce. In the first place, cardiovascular risk factors should be put under control adequately, especially hypertension and diabetes mellitus, both of which contribute to vascular disease. Angiotensin-converting enzyme inhibitors and statins have proven effective to treat these patients. Controlling weight is essential, and a cardiac rehabilitation program can reduce symptoms and improve quality of life.
All types of antianginal drugs can be used in these patients, many times using a trial-and-error approach to it, because patients may be intolerant or drugs ineffective.
To choose the optimal drug therapy we should make a distinction between 2 different profiles of patients with angina pectoris without obstructive coronary artery disease: those with vasospastic angina pectoris and those with microvascular angina pectoris.
Patients with micro- or macrovascular spasm benefit from calcium channel blockers. Both dihydropyridine and non-dihydropyridine drugs can be effective, and the lack of effectiveness of one does not predict a lack of effectiveness of the other. Also, nitrates, both oral an in patches, can be used in this context.
In patients with microvascular angina pectoris not due to vasospasm, beta-blockers, calcium channel blockers, ranolazine, aminophylline, and trimetazidine have given effective results in preliminary trials, but not yet in randomized clinical trials. Although nitrates can be used in this type of patients, it has been proposed that symptoms could become worse.
Finally, antianginal drugs without significant hemodynamic effects can minimize symptoms in both groups of patients, especially ranolazine and trimetazidine.
Q.: With this therapeutic individualization, have any advantages been identified regarding prognosis?
A.: No beneficial effects have been confirmed regarding prognosis in mortality or myocardial infarction. However, fewer events of angina pectoris have been reported leading to a better quality of life, which is essential in these patients. The CorMicA trial10 confirmed that an invasive study of coronary physiology in patients with chest pain and without obstructive coronary artery disease could identify 3 different groups (vasospastic angina pectoris, microvascular angina pectoris, and noncardiac chest pain). Also, that a specific medical strategy for each specific group reduced the occurrence of angina pectoris.
FUNDING
None whatsoever.
CONFLICTS OF INTEREST
None reported.
REFERENCES
1. Arbogast R, Bourassa MG. Myocardial function during atrial pacing in patients with angina pectoris and normal coronary arteriograms. Comparison with patients having significant coronary artery disease. Am J Cardiol. 1973;32:257-263.
2. Lee BK, Lim HS, Fearon WF, et al. Invasive evaluation of patients with angina in the absence of obstructive coronary artery disease. Circulation. 2015;131:1054-1060.
3. Kunadian V, Chieffo A, Camici PG, et al. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology &Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. Eur Heart J. 2020;41:3504-3520.
4. Di Carli MF, Charytan D, McMahon GT, Ganz P, Dorbala S, Schelbert HR. Coronary circulatory function in patients with the metabolic syndrome. J Nucl Med. 2011;52:1369-1377.
5. Panting JR, Gatehouse PD, Yang GZ, et al. Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. N Engl J Med. 2002;346:1948-1953.
6. Caiati C, Montaldo C, Zedda N, et al. Validation of a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) for the evaluation of coronary flow reserve:comparison with intracoronary Doppler flow wire. J Am Coll Cardiol. 1999;34:1193-1200.
7. Hildick-Smith DJ, Maryan R, Shapiro LM. Assessment of coronary flow reserve by adenosine transthoracic echocardiography:validation with intracoronary Doppler. J Am Soc Echocardiogr. 2002;15:984-990.
8. Khav N, Ihdayhid AR, Ko B. CT-Derived Fractional Flow Reserve (CT-FFR) in the Evaluation of Coronary Artery Disease. Heart Lung Circ. 2020;29:1621-1632.
9. Maron DJ, Hochman JS, Reynolds HR, et al.;ISCHEMIA Research Group. Initial Invasive or Conservative Strategy for Stable Coronary Disease. N Engl J Med. 2020;382:1395-1407.
10. Ford TJ, Stanley B, Good R, et al. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina:The CorMicA Trial. J Am Coll Cardiol. 2018;72:2841-2855.
QUESTION: For starters, what is the minimalist approach to transcatether aortic valve implantation (TAVI)?
ANSWER: After the first case described by Cribier et al.1 back in 2002, the management of aortic stenosis through TAVI has consolidated and become a safe and effective therapy that is based on a well-established and standardized procedure. Although it is a complex procedure due to the characteristics of patients and devices and the fact that experienced operators are needed, the growing number of cases reported, and the technological advances made with the devices have improved processes and reduced complications significantly. This has prompted that, over the last few years, certain experienced groups2 have modified certain steps of the procedure and introduced strategies before and after the intervention to simplify and make TAVI more efficient. Also, to promote faster recoveries in the patients. This set of modifications is described as minimalist approach to TAVI. Two of the most significant aspects here are suppressing balloon dilatation and reducing hospital stays. However, there are simplifying strategies that can be divided into 3 parts: previous assessment and case analysis, valve implantation, and postoperative care. During the previous assessment part, the objective is to speed up the study circuits of the patients and reduce the waiting lists. Also, the decision between surgery or TAVI should not be made on the surgical risk but on the risk-benefit ratio based on the patient’s age, comorbidities, functional status, frailty, anatomical characteristics, family support, and on the experience and results of the treating center. Regarding valve implantation, the simplifying strategies are applied in different settings:
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– Healthcare professionals and setting. Procedures can be performed in a cath lab by experienced interventional cardiologists. In cases of transfemoral access, the heart team often includes 2 interventional cardiologists, 2 nurses, and 1 patient care technician. The nurse or the technician is in charge of preparing the device. The presence of 1 anesthesiologist and 1 expert cardiologist in imaging modalities or 1 echocardiographist is advised. With highly selected patients—complex access sites or different from the femoral access, etc.—or if certain complications occur the collaboration of a cardiovascular surgeon may be required.
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– Anesthesia. It is one of the main changes of this minimalist approach. Although the presence of an anesthesiologist during the procedure is advised, general anesthesia is often substituted for local anesthesia and sedation. This avoids intubation and ventilation, minimizes risks, and reduces the hospital stay. General anesthesia would be spared for patients of a higher risk of complications who cannot tolerate the procedure or with high chances of conversion to surgery.
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– Arterial access. In the primary access, the femoral access is often the one used for valve implantation and has given the best results of all. However, there are other alternatives available when it is not feasible. Puncture should be angiography- or ultrasound-guided and percutaneous closure is often performed with devices like Prostar (Abbott Vascular, United States), Perclose Proglide (Abbott Vascular, United States) or Manta (Teleflex, United States). Although the femoral access site is the preferred one in some cases for a direct control of hemostasis, with these devices, percutaneous puncture is a less invasive option that has good results. Regarding secondary arterial access, another arterial access site is often required, usually the contralateral femoral artery, for pigtail catheter insertion to perform the aortography. When inserted into the non-coronary sinus it serves as the reference for implantation. This access site also allows us to advance the protection guidewire inside the artery through which the access occurs in such a way that, if vascular closure is incomplete or fails, on top of providing compression, a balloon can be advanced to occlude the flow and a covered stent can be implanted. To this point, everal minimalist approaches have been suggested: a) use the radial access as the secondary access; b) simplify it by performing a more distal puncture preferably in the common femoral artery 2 cm further down or in the superficial femoral artery. Through 4-Fr or 5-Fr introducer sheath a protection guidewire would be advanced to perform selective injections, and c) with the smaller size of today’s sheath some even suggest inserting a protection guidewire.
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– Echocardiogram. Using transthoracic echocardiography during implantation is considered enough because it avoids the problems associated with the transesophageal echocardiogram and allows us to assess fundamental aspects such as LV contractility, the position of the guidewire, and the outcome of valve implantation. Also, complications like cardiac tamponade, aortic regurgitation, etc can be discarded.
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– Transient pacemaker. Rapid ventricular pacing is required for balloon-expandable valve and certain self-expandable valve implantation. Balloon-tipped electrode catheters should be used to reduce the risk of perforation. To avoid the problems associated with catheterizing that venous route, a metal guidewire placed in the left ventricle can be used for pacing purposes. After placing a subcutaneous 22G needle close to the sheath, the clips are connected to the needle (positive) and the ventricle metal guidewire (negative) isolated with a catheter or a valve placed close to the annulus. If there is no AV block (transient or permanent) or QRS widening > 160 m the pacemaker is removed in the cath lab after analyzing the electrocardiogram. If a definitive pacemaker is required, it should be implanted within the next 72 hours to avoid unnecessary longer the hospital stays.
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– Avoid balloon predilatation. With some of the new valves available it is possible to perform direct valve implantation, thus reducing the risks derived from aortic valvuloplasty.
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– Avoid urinary catheterization. It reduces hospital complications—infections, hematuria—and the hospital stay.
Regarding the third part, postoperative care, it is necessary to monitor the patient closely within the first few hours by closely assessing his hemodynamic status and the vascular access routes. Follow-up blood tests should be performed to detect blood losses. Also, the heart rhythm should be monitored to rule out the presence of cardiac conduction disorders or new-onset arrhythmias. A control echocardiogram is required the next day and, in the absence of complications, the patient should regain mobilization soon.
Q.: What advantages does deep sedation have over general anesthesia and how do you think it should be performed?
A.: The presence of an anesthesiologist in the cath lab guarantees closer monitoring and brings comfort to the patient. It also speeds up the procedure in case of complications. This does not necessarily imply using general anesthesia in every case: the use of conscious sedation and local anesthesia allows us to avoid orotracheal intubation, brings greater hemodynamic stability, and shorter procedural and recovery times. Several studies have proven the safety profile of this type of sedation with similar rates of mortality and complications;3,4 its use has become very popular over the last few years. For example, in France,5 it was used in 30% of the cases in 2010 up to 70% in 2017. Therefore, general anesthesia would be spared for patients with hemodynamic instability and higher risk of complications who don’t tolerate the procedure or have high chances of conversion to surgery.
Q.: How is echocardiographic imaging implemented during TAVI? Always or occasionally? Transthoracic or transesophageal?
A.: Having a cardiologist expert in cardiac imaging modalities performing monitorization tasks through transthoracic echocardiogram brings extra safety, and avoids the problems associated with the transesophageal echocardiogram. This expert can control the position of the guidewire inside the ventricle, confirm the results of implantation by assessing gradients, identify some degrees of aortic regurgitation, and detect rapidly possible complications that may occur like abnormalities in cardiac contractility or the appearance of pericardial effusion. Transesophageal echocardiogram would be spared for cases of poor acoustic window or specific needs.
Q.: There are very different vascular occlusion systems available. Are there significant differences to pick one over the other based on certain characteristics of the patient? Which are the preferences of your heart team?
A.: Different suture-mediated closure devices (Proglide, Prostar) or collagen-based devices (Manta)6,7 can be used with good results. Some may be used based on the preferences or experience of the heart team since the comparative studies conducted so far do not make any clear differences on this regard. Suture-mediated closure devices may have more problems in femoral arteries with calcium deposits while the Manta collagen-based devices can present complications in small-caliber femoral arteries (< 6 mm) or in very obese patients. Also, we should take into consideration the cost of each one of these devices, and the necessary learning curves. The single or double Proglide device is the most widely used. As a matter of fact, the latter is the common strategy in our center. None of them is infallible and in the presence of bleeding a balloon is required for occlusion purposes and even covered stent graft implantation to contain the bleeding.
Q.: Which is the average hospital stay after TAVI at your center? What do you think of 24 to 48-hour early hospital discharges?
A.: In our center, the average hospital stay is between 3 and 4 days because, although we try to discharge the patients 48 hours after the procedure, their risk profile often requires longer hospital stays. The patient should regain mobility within a few hours if the transient pacemaker has been removed and there are no vascular access complications. Therefore, uncomplicated patients can be discharged in < 72 hours. This early hospital discharge has proven feasible and safe in different studies and even in 1 meta-analysis that confirmed the good results of discharging patients within 3 days.8 Next-day faster hospital discharges are also possible in highly selected patients without procedural complications.9 However, a reason for concern in these patients is the possibility of developing AV block, and the need for pacemaker implantation. Although 50% of cardiac conduction disorders occur during implantation, 44% of them occur within the next 3 days.10 If the 24-hour discharge is decided, it should be performed with a protocol of electrocardiographic monitoring and early detection of patients requiring pacemaker.11
Q.: Finally, in your own opinion, what patients would be eligible for minimalist TAVI and when is it ill-advised?
A.: It is going to depend on how experienced the heart team is, on the characteristics of the hospital, and on the situation of the patient always taking into consideration that the primary endpoint here is the safety and effectiveness of the procedure. The minimalist approach is a reasonable option in hemodynamically stable patients with adequate femoral accesses, collaborators, and without additional problems involving a high risk of complications like coronary occlusion. It will be gradually implemented, yet the effectiveness and quality of healthcare should not be compromised. Instead, the procedures should be performed faster, better, and adapted to the needs of the patients to avoid unnecessary tests, maneuvers, and stays.
FUNDING
None reported.
CONFLICTS OF INTEREST
None reported
REFERENCES
1. Cribier A, Eltchaninoff H, Bash A, et al. Percutaneous Transcatheter Implantation of an Aortic Valve Prosthesis for Calcific Aortic Stenosis First Human Case Description. Circulation 2002;106:3006-3008.
2. Lauck SB, Wood DA, Baumbusch J, et al. Vancouver Transcatheter Aortic Valve Replacement Clinical Pathway:Minimalist Approach, Standardized Care, and Discharge Criteria to Reduce Length of Stay. Circ Cardiovasc Qual Outcomes. 2016;9:312-321.
3. Ehret C, Rossaint R, Foldenauer AC, et al. Is local anaesthesia a favourable approach for transcatheter aortic valve implantation?A systematic review and meta-analysis comparing local and general anaesthesia. BMJ Open. 2017;7:e016321.
4. Harjai KJ, Bules T, Berger A, et al. Efficiency, Safety, and Quality of Life After Transcatheter Aortic Valve Implantation Performed With Moderate Sedation Versus General Anesthesia. Am J Cardiol. 2020;125:1088-1095.
5. Oguri A, Yamamoto M, Mouillet G, et al. FRANCE 2 Registry Investigators. Clinical outcomes and safety of transfemoral aortic valve implantation under general versus local anesthesia:subanalysis of the French Aortic National CoreValve and Edwards 2 registry. Circ Cardiovasc Interv. 2014;7:602-610.
6. Mehilli J, Jochheim D, Abdel-Wahab M, et al. One-year outcomes with two suture-mediated closure devices to achieve access-site haemostasis following transfemoral transcatheter aortic valve implantation. EuroIntervention. 2016;12:1298-1304.
7. De Palma R, Settergren M, Rück A, et al. Impact of percutaneous femoral arteriotomy closure using the MANTATM device on vascular and bleeding complications after transcatheter aortic valve replacement. Catheter Cardiovasc Interv. 2018;92:954-961.
8. Kotronias RA, Teitelbaum M, Webb JG, et al. Early Versus Standard Discharge After Transcatheter Aortic Valve Replacement. A Systematic Review and Meta-Analysis. JACC Cardiovasc Interv. 2018;11:1759-1771.
9. Kamioka N, Wells J, Keegan P, et al. Predictors and clinical outcomes of next-day discharge after minimalist transfemoral transcatheter aortic valve replacement. JACC Cardiovasc Interv. 2018;11:107-115.
10. Bagur R, Rodés-Cabau J, Gurvitch R, et al. Need for permanent pacemaker as a complication of transcatheter aortic valve implantation and surgical aortic valve replacement in elderly patients with severe aortic stenosis and similar baseline electrocardiographic findings. JACC Cardiovasc Interv. 2012;5:540-551.
11. Naveh S, Perlman GY, Elitsur Y, et al. Electrocardiographic predictors of long-term cardiac pacing dependency following transcatheter aortic valve implantation. J Cardiovasc Electrophysiol. 2017;28:216-223.
- Debate: Minimalist approach to TAVI as a selective strategy
- Debate: Intervention on the mitral and the tricuspid valves. Perspective from surgery
- Debate: Intervention on the mitral and the tricuspid valves. Perspective from interventional cardiology
- Debate: Percutaneous left atrial appendage closure. The interventional cardiology 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