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: Although we will discuss the aspects of 2 plaque modification techniques, please explain when you resort to intravascular imaging modalities in cases of calcified lesions and how that helps you.
ANSWER: Undoubtedly, intracoronary imaging modalities are an essential tool for interventional cardiologists in dealing with the assessment and treatment of calcified lesions. As we all know, revascularization of these lesions is associated with a higher rate of short- and long-term cardiovascular events, related to a greater risk of stent underexpansion and intraoperative complications.1 In calcified lesions, simple angiographic assessment is insufficient because of its lower sensitivity in the detection of coronary artery calcification, and limitations in the identification of calcium distribution patterns.
In my opinion, since optimizing results is so important, the use of intravascular ultrasound or optical coherence tomography is mandatory in cases of moderate or severe calcification and helps us in several key aspects of the procedure. First, both intravascular ultrasound and optical coherence tomography have high sensitivity and specificity for calcium detection and its morphological characterization: pattern (nodular, parietal), angle, extent, and depth. With this information, we can select the best plaque modification technique for each case and evaluate its effect on the treated lesion. In recent years, several risk scores based on intracoronary imaging modalities have been developed, including decision algorithms for plaque modification systems based on calcium length, depth, and angle.2
Finally, imaging modalities allow us to be precise in selecting the size and length of the stent, as well as to assess its apposition and expansion, and rule out complications and residual disease. This aspect is crucial in the management of calcified lesions, where plaque modification devices can cause deep dissections and fractures, and we encounter more difficulties when trying to achieve adequate stent expansion.
Q.: In your opinion, what are the advantages and disadvantages of intracoronary lithotripsy?
A.: One of the main advantages for the implementation of intracoronary lithotripsy in the daily routine of cath labs is that it is technically simple and reproducible and does not require a long learning curve. The currently available intracoronary lithotripsy (ICL) system—Shockwave Medical, United States—consists of a specific semicompliant rapid-exchange balloon catheter with a 0.042-inch crossing profile, which is advanced inside the coronary arteries through a conventional 0.014-inch guidewire, and is compatible with a 6-Fr guide catheter. Once positioned in the lesion, the balloon is inflated to 4 atm with the sole intention of ensuring good contact between its surface and the vascular wall to facilitate energy transfer. Inside the balloon, there are 2 emitters that receive an electric discharge from the generator, vaporizing the liquid inside and generating sound waves that cause a local effect. The waves run through the soft tissues, causing selective calcium microfractures in the intimal and medial layers of the vascular wall. After pulse emission and the corresponding calcium modification, the balloon is inflated at 6 atm to maximize luminal gain.
On the other hand, compared with the limitations of noncompliant, very high-pressure, or cutting balloons, which in eccentric calcification can be directed toward noncalcified arterial segments with a risk of dissection at the fibrocalcific interface, ICL allows homogeneous calcium fracture. Another advantage is that ICL avoids the bias of having to follow the direction of the guidewire of rotational and orbital atherectomies, because it fractures calcium on superficial and deep layers circumferentially through acoustic pressure waves.3
Regarding complications, calcium fragmentation caused by the lithotripsy balloon remains in place, without distal embolization, thus reducing the incidence of slow-no reflow.4
In terms of disadvantages, the main limitation of ICL is its crossing profile: it often requires lesion predilatation or combination with atherectomy techniques. Notably, the DISRUPT CAD III trial5 reported ventricular captures during ICL pulses in 41.1% of the patients. Although the drop in systolic pressure is more common in patients in whom ICL induces ventricular capture, it has not been associated with the occurrence of adverse events, or sustained ventricular arrhythmias.
Q.: In which cases do you use intracoronary lithotripsy as a first-line approach?
A.: The available evidence on ICL comes from the DISRUPT CAD trials.5-8 The most relevant of these trials, the DISRUPT CAD III,5 is a prospective registry of 431 patients that assessed the safety and efficacy profile of the ICL balloon to treat calcified lesions. The 30-day rate of adverse cardiovascular events (death, myocardial infarction, or target lesion revascularization) was 7.8%, and the effectiveness rate (procedural success with in-stent stenosis < 50%) was 92.4%. This trial included patients with severely calcified de novo lesions and excluded those with acute myocardial infarction and aorto-ostial or bifurcation lesions.
As I mentioned previously, with the data provided by imaging modalities on calcium distribution and depth, we could consider ICL as the first-line approach to treat concentric calcified lesions with circumferential calcium distribution, especially in cases of deep calcium deposits, where ICL has proven more effective than other plaque modification techniques. Furthermore, ICL is effective in large-caliber vessels since balloons can be up to 4 mm in diameter.
One of the most common scenarios in which ICL is used in routine clinical practice is in calcified lesions that cannot be dilated with conventional or high-pressure balloons. This indication accounts for up to 75% of the cases in real-world registries,9 with very good results, and a procedural success rate of 99%.
Q.: Which calcified lesions benefit most from intracoronary lithotripsy compared with rotational or orbital atherectomy?
A.: While we can’t draw direct comparisons on the safety and efficacy results between ICL and rotational or orbital atherectomy because of the different inclusion criteria, stent types, and study endpoints among trials such as ROTAXUS10 and DISRUPT-CAD, in clinical practice, we choose one technique over the other based on the characteristics of the lesion.
Although, as I will discuss later, both techniques are complementary, atherectomy is an excellent option to treat balloon-uncrossable calcified lesions. However, atherectomy targets superficial calcium shaving, less so the deep calcium deposits. Hence, ICL is a better choice for concentric calcified lesions with circumferential and deep calcium distribution.
Beyond the landmark studies, in recent years, numerous real-world experiences11 have been reported, demonstrating the usefulness of ICL in specific and complex scenarios, such as:
- – Calcified bifurcation lesions: information on the safety and efficacy profile of ICL in complex contexts is limited to case reports and short series of patients describing experiences in substrates such as bifurcation or aorto-ostial lesions with promising results. Unlike rotational or orbital atherectomy techniques, ICL is increasingly used because it allows us to work with 2 different guidewires easily and simplifies the procedure in this context.
- – In-stent stenosis: Although this is an off-label use of ICL, there is growing evidence of the usefulness of ICL in both acute stent underexpansion and restenosis, especially in nondilatable lesions due to calcified neoatherosclerosis.12 In the Spanish multicenter REPLICA registry13 of 426 patients treated with ICL in routine clinical practice, a previously implanted stent was stenosed in 23% of the cases.
- – Chronic occlusions: ICL can be useful to treat chronic occlusions with severe calcification, and its use has increased in recent years, as confirmed by a recently published subanalysis of the PROGRESS-CTO registry14 with data from 82 patients (out of a total of 3301 included in the study [2.5%]) who underwent ICL. Indications were severe vessel calcification, or balloon nondilatable lesions. Technical success was achieved in 94% of the patients and procedural success in 90%.
- – Acute coronary syndrome: available data on the use of ICL in calcified lesions in patients with acute coronary syndrome are scarce. These cases were excluded from the DISRUPT-CAD trials, and again, the experience reported in the medical literature is limited to short case series. However, as the REPLICA registry results show, where a high percentage of patients with calcified lesions treated with ICL presented with acute coronary syndrome (62.8%), this technique is commonly used in the routine clinical practice in this group of patients who require a quick and safe technique.
Q.: How do you integrate the 2 techniques into your protocol to treat calcified lesions?
A.: The combined use of the ICL balloon and other plaque modification techniques, such as rotational15 or orbital atherectomy,16 has shown promising results in short patient series, and seems to be a highly attractive strategy when the target lesion cannot be reached with the ICL balloon.
In my opinion, the combination of atherectomy and ICL techniques is a suitable option to treat diffuse, superficial, and deep calcium deposits. By combining the 2 techniques, we can leverage the advantages of each. On the one hand, atherectomy allows the advancement of the ICL balloon in long lesions with severe stenosis that prevent its passage. On the other, ICL is very useful in balloon nondilatable lesions after atherectomy. This combination of techniques can be particularly useful in one of the most complex scenarios: the management of calcium nodules.
FUNDING
None declared.
STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE
Artificial intelligence was not used in the preparation of this article.
CONFLICTS OF INTEREST
None declared.
REFERENCES
1. Généreux P, Redfors B, Witzembichler B, et al. Two year outcomes after percutaneous coronary intervention of calcified lesions with drug eluting stents. Int J Cardiol. 2017;231:61-67.
2. Fujino A, Mintz G, Matsumura M, et al. A new optical coherence tomography-based calcium scoring system to predict stent underexpansion. EuroIntervention. 2018;13:e2182-e2189.
3. Jurado-Román A, Gómez-Menchero A, Gonzalo N, et al. Documento de posicionamiento de la ACI-SEC sobre la modificación de la placa en el tratamiento de las lesiones calcificadas. REC Interv Cardiol. 2023;5:43-61.
4. Rodriguez Costoya I, Tizón Marcos H, Vaquerizo Montilla B, et al. Coronary Lithoplasty:Initial Experience in Coronary Calcified Lesions. Rev Esp Cardiol. 2019;72:788-790.
5. Hill J, Kereiakes DJ, Shlofmitz RA, et al. Intravascular lithotripsy for treatment of severely calcified coronary artery disease. J Am Coll Cardiol. 2020;76:2635-2646.
6. Brinton TJ, Ali ZA, Hill JM, et al. Feasibility of Shockwave Coronary Intravascular Lithotripsy for the Treatment of Calcified Coronary Stenoses. Circulation. 2019;139:834-836.
7. Ali ZA, Nef H, Escaned J, et al. Safety and effectiveness of coronary intravascular lithotripsy for treatment of severely calcified coronary stenoses:the Disrupt CAD II study. Circ Cardiovasc Interv. 2019;12:e008434.
8. Saito S, Yamazaki S, Takahashi A, et al. Intravascular lithotripsy for vessel preparation in severely calcified coronary arteries prior to stent placement —primary outcomes from de Japanese Disrupt CAD IV Study. Circ J. 2022;85:826-833.
9. Azir A, Bhatia G, Pitt M, et al. Intravascular lithotripsy in calcified-coronary lesions:A real-world observational, European multicenter study. Catheter Cardiovasc Interv. 2021;98:225-235.
10. Abdel-Wahab M, Richardt G, Joachim Buttner H, et al. High-speed rotational atherectomy before paclitaxel-eluting stent implantation in complex calcified coronary lesions:the randomized ROTAXUS (Rotational Atherectomy Prior to Taxus Stent Treatment for Complex Native Coronary Artery Disease) trial. JACC Cardiovasc Interv. 2013;6:10-19.
11. Vilalta V, Rodriguez-Leor O, Redondo A, et al. Litotricia coronaria en pacientes de la vida real:primera experiencia en lesiones complejas y gravemente calcificadas. REC Interv Cardiol. 2020;2:76-81.
12. Tovar N, Sardella G, Salvi N, et al. Coronary litotripsy for the treatment of underexpanded stents:CRUNCH registry. Eurointervention. 2022;18:574.8112.
13. Rodriguez-Leor O, Cid-Alvarez AB, Lopez-Benito M, et al. A Prospective, Multicenter, Real-World Registry of Coronary Lithotripsy in Calcified Coronary Arteries: The REPLICA-EPIC18 Study. JACC Cardiovasc Interv.. 2024:76(12):1021-1031.
14. Kostantinis S, Simsek B, Karaksonyi J, et al. Intravascular lithotripsy in chronic total occlusion percutaneous coronary intervention:Insights from the PROGRESS?CTO registry. Catheter Cardiovasc Interv. 2022;100:512-519.
15. Gonzalvez-Garcia A, Jimenez-Valero S, Galeote G, et al. “RotaTripsy”:combination of rotational atherectomy and intravascular lithotripsy in heavily calcified coronary lesions:a case series. Cardiovasc Revasc Med. 2022;35:179-184.
16. Yarusi BB, Jagadeesan VS, Hussain S, et al. Combined coronary orbital atherectomy and intravascular lithotripsy for the treatment of severely calcified coronary stenoses:the first case series. J Invasive Cardiol. 2022;34:E210-E217.
QUESTION: Can the prevalence of asymptomatic aortic stenosis and its various degrees of severity be estimated in the general population?
ANSWER: Although estimates can be made, they undoubtedly underestimate the true prevalence of asymptomatic aortic stenosis (AS). What we know is that, according to the 2017 European Cardiovascular Disease Statistics, over 6 million new cases of cardiovascular disease are diagnosed each year in Europe, with over 50 million prevalent cases (a 30% increase since 2000). In Spain, this amounts to over 250 000 new cases of cardiovascular disease diagnosed each year, and over 4 million prevalent cases.
If we focus on valvular heart disease, according to the latest Euro Heart Survey, AS is still the most widely diagnosed (41%) and frequently treated (45% of all procedures performed) severe valvular heart disease in the hospital setting. Undoubtedly, AS represents the highest burden of valvular heart disease among patients overall, and is even more significant among older adults. In the Olmsted County registry,1 the prevalence of AS was 0.5% (4.6% in patients older than 75 years, a rate very similar to that of the AGES-Reykjavík trial,2 where the prevalence of severe AS in patients older than 70 years was 4.3%.)
If we look at asymptomatic patients, data on the true prevalence are available but they are drawn from indirect sources. Spain has played a major role in our ability to estimate the prevalence in these patients. In the registry of Ferreira et al.3 the prevalences of sclerosis was 45.5% and that of stenosis was 3%. More recently, a study conducted by our group4,5 in vaccination centers found undetected aortic sclerosis in 53.4% of the patients and undetected AS in and 4.2%.
Therefore, based on the population prevalence data obtained and the current and projected composition of the Spanish population for the next 40 years, it is estimated that 470 000 Spaniards currently have undiagnosed AS. If the expectations for population growth and distribution of Spain’s National Statistics Institute are met, and if the proportion of diagnosed or treated cases vs undetected cases doesn’t change, the number of people with undiagnosed AS would be close to 1 million by 2060. If we assume that 10% of all undetected cases of AS are severe, were talking about nearly 100 000 cases of undiagnosed severe AS and, therefore, not followed-up or potentially treated. Let’s not forget that, currently, nearly 4500 cases of severe AS are treated each year, which helps put the problem in perspective.
Q.: How should patients with severe AS who remain asymptomatic be approached from a diagnostic standpoint?
A.: First, it is essential to make sure that a patient with severe AS is truly asymptomatic. The key is to delve deep into the patient’s past medical history and have an expert review the EKG performed. If stenosis is genuinely severe and asymptomatic, there are data that will eventually lead us to start early treatment. We should remember to assess the presence of ventricular dysfunction, symptom onset during exercise, a fall in blood pressure on exertion, marked elevations of brain natriuretic peptide levels, very extensive coronary artery calcification, and rapid reduction in aortic area during disease progression; these are clear indications that we need to act quickly. This is much more important with today’s well-established, low-risk percutaneous techniques. We should remember that, with the rapid advancement of the technique since the introduction of transcatheter aortic valve implantation (TAVI), practices that we never thought to question, such as waiting for symptom onset or starting treatment before progression to severe disease, may have become outdated.
I think that the best time to treat asymptomatic patients with severe AS is when they develop left ventricular decompensation. Data such as brain natriuretic peptide levels, the EKG strain pattern, T1 mapping, and delayed enhancement on magnetic resonance imaging help identify high mortality risk in these patients. Therefore, stratifying heart damage adds additional prognostic value to the traditional clinical risk factors for predicting survival in asymptomatic AS.
Ongoing trials6,7 may lead us to consider earlier interventions even in asymptomatic patients.
Q.: What relevant evidence could support the use of aortic valve replacement in a case of truly asymptomatic severe aortic stenosis?
A.: There is evidence from patients who underwent surgery that supports the idea of treating asymptomatic patients. The AVATAR trial8 demonstrated that, in asymptomatic patients with severe AS, early surgery reduced the composite primary endpoint of all-cause mortality, acute myocardial infarction, stroke, and heart failure-related admissions compared with conservative treatment.
The EARLY TAVR trial (NCT03042104) will examine the safety and efficacy profile of TAVI with the SAPIEN 3 or SAPIEN 3 Ultra valves vs clinical follow-up in asymptomatic patients with severe AS. The aim of this trial is to compare outcomes between patients undergoing valve replacement early in the disease and those undergoing clinical surveillance.
However, given the natural progression of AS and the low morbidity and mortality of TAVI, the idea of treating AS at an earlier stage of the disease has been suggested. The recent VALVENOR trial9 demonstrated that, compared with the general population, patients with moderate symptomatic AS had more cardiovascular mortality than those with mild AS (although still lower than that of patients with severe AS). In this regard, the PROGRESS (NCT04889872), TAVR UNLOAD (NCT02661451), and landmark EXPAND TAVR II trials (NCT05149755) assess TAVI vs clinical surveillance in symptomatic patients with moderate AS. While cautious optimism is warranted, it’s important to acknowledge certain potential limitations. Also, we must be aware that preventing valve degeneration is an important area of current research and that replacing the native valve with a prosthetic valve is not a permanent solution to the problem. Additionally, as we treat progressively younger patients, it is important to understand the anatomical limitations imposed by the need for future valve-in-valve procedures and the durability of the valves.
Q.: How does your center currently manage these patients?
A.: It’s obvious that our center has radically changed the diagnosis, follow-up, and treatment of these patients since we set up the Valve Clinic (2 clinical cardiologists and 1 heart valve clinical nurse specialist) 7 years ago. Diagnoses are reached following a standardized protocol and always with the same echocardiography machine, which is configured to only perform valve EKGs. This guarantees acceptable variability and standardization. Once the clinical cardiologist has decided that a patient needs treatment, we stay in close contact with other professionals specialized in the management of this type of patient. This undoubtedly enhances the quality of care. Data are reported to the hospital annually and are then published, including all possible complications and outcomes. Surgeons also present data on their surgically-treated patients on a yearly basis. We’re lucky to have excellent clinical cardiologists, operators, and surgeons at Hospital Ramón y Cajal with broad experience in the management of patients with valvular heart disease and with published data that can be audited.
FUNDING
None declared.
STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE
No artificial intelligence has been used in the preparation of this work.
CONFLICTS OF INTEREST
J.L. Zamorano has not received any funding for drafting this article. He has received speaker fees from Bayer, Pfizer, Daichii, and Novartis.
REFERENCES
1. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases:a population-based study. Lancet. 2006;368:1005-1011.
2. Danielsen R, Aspelund T, Harris TB, Gudnason V. The prevalence of aortic stenosis in the elderly in Iceland and predictions for the coming decades:The AGES-Reykjavík study. Int J Cardiol. 2014;176:916-922.
3. Ferreira-González I, Pinar-Sopena J, Ribera A, et al. Prevalence of calcific aortic valve disease in the elderly and associated risk factors:a population-based study in a Mediterranean area. Eur J Prev Cardiol. 2013;20:1022-1030.
4. Ramos J, Monteagudo JM, González-Alujas T, et al. Large-scale assessment of aortic stenosis:facing the next cardiac epidemic?Eur Heart J Cardiovasc Imaging. 2018;19:1142-1148.
5. Ramos Jiménez J, Hernández Jiménez S, Viéitez Flórez JM, Sequeiros MA, Alonso Salinas GL, Zamorano Gómez JL. Cribado poblacional de estenosis aórtica:prevalencia y perfil de riesgo. REC CardioClinics. 2021;56:77-84.
6. Lancellotti P, Magne J, Dulgheru R, et al. Prognostic impact of left ventricular ejection fraction in patients with severe aortic stenosis. JACC Cardiovasc Interv. 2018;11:145157.
7. Bohbot Y, de Meester de Ravenstein C, Chadha G, et al. Relationship between left ventricular ejection fraction and mortality in asymptomatic and minimally symptomatic patients with severe aortic stenosis. JACC Cardiovasc Imaging. 2019;12:38-48.
8. Banovic M, Putnik S, Penicka M, et al. Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis:The AVATAR Trial. Circulation. 2022;145:648-658.
9. Coisne A, Montaigne D, Aghezzaf S, et al. Association of mortality with aortic stenosis severity in outpatients. JAMA Cardiol. 2021;6:1424-1431.
QUESTION: What relevant evidence could support aortic valve replacement today in cases of true severe asymptomatic aortic stenosis? Are there any studies on both techniques, surgery and transcatheter implantation?
ANSWER: Ross and Braunwald’s1 description of the outcomes of patients with severe symptomatic aortic stenosis (AS) almost 60 years ago laid the foundations for the indication for surgery—the first-line therapy to date—to treat this disease, although transcatheter aortic valve implantation (TAVI) is also indicated. At a time when surgery was the only therapeutic option available, with mortality rates close to 3% to 4%, nobody thought of treating asymptomatic patients, who had a risk of sudden death of nearly 1%. These findings were confirmed by later studies, and the treatment of asymptomatic AS continued to lack evidence until the first decade of the 21st century when observational studies with small series of patients with severe asymptomatic AS (Vmax ≥ 4 m/s and mean gradient ≥ 40 mmHg) began to be published. In all of them, the results favored early surgical treatment. In the study of 197 patients by Kang et al.,2 the primary endpoint was a composite of operative and follow-up mortality. The 6-year cardiac and all-cause mortality rates were 0% and 2 ± 1% in the surgical group compared with 24 ± 15% to 32 ± 6% in the conservative treatment group. The CURRENT AS3 registry of Taniguchi et al, with 1808 patients (291 in the surgical group and 1517 in the conservative treatment group) favored the surgical group in terms of overall mortality (15.4% vs 26.4%; P < .009) and heart failure-related admissions (3.8% vs 19.9%; P < .0001). The only randomized clinical trials published to date comparing conservative vs surgical treatment are the RECOVERY4 and the AVATAR5 trials, both with a small number of patients (145 and 157, respectively), and both with results favorable to surgery. In the RECOVERY trial, the primary endpoint was a composite of procedural and cardiovascular mortality during follow-up, with rates of 1% in the surgical group and 15% in the conservative treatment group (hazard ratio [HR], 0.09; 95%CI, 0.01-0.67). The 4- and 8-year cumulative incidence rates of the primary endpoint remained at 1% in the surgical group vs 6% and 26% (P = .003) in the conservative treatment group. In the AVATAR trial, the primary endpoint was a composite of all-cause mortality, myocardial infarction, stroke, or unplanned heart failure-related admission, with rates of 15.22% and 34.7% at the 3-year follow-up (HR, 0.46; 95%CI, 0.23-0.9).
The first TAVI was performed back in 2002. Since then, we have come a long way regarding indications—although it’s only a short time—because in 20 years, TAVI has been recognized as the treatment of choice for inoperable and high surgical risk patients, with similar results compared to those of surgery in moderate and low surgical risk patients. These trials have focused on symptomatic patients. Several trials are under way in asymptomatic patients, EARLY TAVR (NCT03042104) and EVOLVED (NCT03094143), and their results will be published soon, but until then, the only evidence to date supporting treatment in asymptomatic patients is surgical.
Q.: When the decision is made to intervene in cases of severe asymptomatic aortic stenosis, on what grounds should the choice be made between surgery and TAVI? Would it be any different from the choice in a symptomatic case?
A.: The current clinical guidelines on the management valvular heart disease of the European Society of Cardiology6 still focus on the indication for treating AS based on symptoms; asymptomatic AS is not included in this indication, unless there are laboratory or echocardiographic predictors of rapid symptom progression. As explained earlier, there is currently more evidence on surgery in asymptomatic patients. However, a more in-depth analysis of the studies reveals 2 important facts. One is that the mean age was generally low: 65 years in the RECOVERY trial and 68 years in the AVATAR trial, and was very similar in registries. The other is that the causes of AS are highly variable: in the RECOVERY trial, 61% of the patients had bicuspid valves, 33% degenerative valves, and 6% rheumatic valves. In the AVATAR trial, 84.7% had degenerative valves, 14% bicuspid valves, and 1% rheumatic valves.
In Spain, where life expectancy is one of the longest worldwide—82 years in men and 87 years in women in 2023—most patients treated with TAVI have degenerative AS, and the incidence of bicuspid valves is lower than that reported by studies, which means that using the same criteria is challenging. However, it seems clear that severe or very severe AS, as included in the studies, shows better mid- and long-term survival rates when treated early, while asymptomatic. The severity criteria included in the studies (Vmax ≥ 4.5 m/s, mean gradient ≥ 50 mmHg) help us select those patients who benefit the most from early treatment. On the issue on what treatment we should use (surgery or TAVI), the decision is more complicated due to the lack of evidence on TAVI. As mentioned earlier, the average patients we treat are octogenarians. In some cases, AS is found during a routine examination, and if they are truly asymptomatic (because octogenarians often cut down on activity and have difficulty recognizing their own physical limitations) and meet severity criteria, an early intervention will result in better quality of life and fewer procedural complications. In my opinion, applying the same criteria used with symptomatic patients is beneficial for patients, meaning that, in patients with low-to moderate surgical risk, if we accept the results of TAVI trials,6-8 the transcatheter option is entirely acceptable. A different type of patient are those under follow-up because they have bicuspid valves or rheumatic disease. These patients are often younger and the indication for surgical valve replacement is clearer because TAVI still has limitations that need to be resolved in terms of durability, the need for new procedures if there is prosthetic valve degeneration, access to coronary arteries, and the treatment of bicuspid valves, which also remains poorly established. Additionally, TAVI is associated with a higher rate of pacemaker implantation, which, in young patients, is related to new comorbidities and various effects on ventricular function.
Therefore, the choice would be TAVI for octogenarians and surgery for younger patients. I would set patients from 75 to 80 years apart who could potentially receive transcatheter treatment based on their own preferences.
On the issue of whether treatment would differ in asymptomatic compared with symptomatic patients, in my opinion, this would not be the case. AS is a continuum in which symptoms appear sooner or later. Although it seems that we can base our decisions on evidence when treating symptomatic AS, we have to think that the benefit to the patient is greater as physical and pathophysiological conditions will always be better before symptom onset. In fact, sometimes the changes triggered by symptomatic AS can be irreversible. Treating asymptomatic patients requires both us and surgeons, who have already reduced mortality down to 1% in these patients, more meticulous approaches regarding valve selection and implantation, correctly selecting the valve while minimizing risks and complications, since patients should benefit in the short- and long-term.
Q.: Any considerations on the TAVI technique that should be used in these cases?
A.: When we decide to perform TAVI in a symptomatic patient, we assess the anatomical and clinical factors involved. The same applies to asymptomatic patients: on the one hand, if the patient is young and has a bicuspid valve, the valve selected should have enough radial strength, a low pacemaker implantation rate, and give us room to plan a second TAVI in the future while securing access to the coronary arteries. If a self-expanding supra-annular valve is selected, the current tendency is to place the prosthetic valve as high as possible with respect to the annulus to minimize the risk of pacemaker implantation. This may compromise access to the coronary arteries, which is why, commissural alignment should be attempted, as far as possible. To avoid complications such as stroke, which can be devastating in young patients, the use of embolic protection devices is justified, although the only randomized clinical trial published to date has not shown any benefits in specific subgroups for stroke in general (primary endpoint) as opposed to disabling stroke (not the primary endpoint). In older asymptomatic patients with degenerative AS, the implantation technique follows the same pattern used with symptomatic patients.
Q.: What is the current management of these patients in your center?
A.: At the Álvaro Cunqueiro Hospital, all patients are discussed in a heart team session, where the treatment criteria are more or less clear. Asymptomatic patients come through various routes: one is patients with valvular heart disease under clinical surveillance who develop severity criteria during follow-up. If the patient is older than 80 years, the decision is often to use the transcatheter approach, from 75 to 79 years, either of the 2 treatments would be fine, and the patient’s preference is a consideration, and if the patient is younger than 75 years, the decision is often to perform surgical valve replacement. Patients with bicuspid valves are often young and initially referred for surgical treatment.
In other patients, AS is found during routine examination due to another disease. Here, there’s a subgroup that requires quick decision-making: patients with neoplasms or interventions that cannot be delayed for too long. In these cases, transcatheter treatment is the chosen one because implantation is possible once the results from the computed tomography become available. The intervention is performed within the next few days, with rapid recovery, before the next intervention. If the patient is young and has a bicuspid valve, a balloon-expandable valve is often used. If the patient is older and doesn’t have coronary artery disease, a self-expanding valve is used. If the patient has coronary artery disease to be treated after the intervention, if necessary, a self-expanding valve with easy access to the coronary arteries is often implanted. If vascular access is suboptimal, a self-expanding valve is also the preferred choice due to its better profile.
If asymptomatic patients don’t have any other conditions requiring immediate treatment, they are treated as if they were symptomatic patients, except for patients with criteria of very severe AS (Vmax ≥ 5 m/s, mean gradient ≥ 60 mm Hg, and progression of Vmax ≥ 0.3 m/s/year), who are treated preferentially.
FUNDING
None declared.
STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE
No artificial intelligence has been used in the preparation of this work.
CONFLICTS OF INTEREST
J. A. Baz Alonso is a proctor for Biosensors for the Allegra valve implantation, and advisor to Medtronic Iberia on structural heart diseases.
REFERENCES
1. Ross J, Braunwald E. Aortic stenosis. Circulation. 1968;38 suppl V:61-67.
2. Kang DH, Park SCJ, Rim JH, et al. Early surgery versus conventional treatment in asymptomatic very severe aortic stenosis. Circulation. 2010;121:1502-1509.
3. Taniguchi T, Morimoto T, Shiomi H, et al. Initial surgical versus conservative strategies in patients with asymptomatic severe aortic stenosis. J Am Coll Cardiol. 2015;66:2827-2838.
4. Kang D-H, Park S-J, Lee S-A, et al. Early surgery or conservative care for asymptomatic aortic stenosis. N Engl J Med. 2020;382:111-119.
5. Banovic M, Putnik S, Penicka M, et al. Aortic valve replacement versus conservative treatment in asymptomatic severe aortic stenosis:the AVATAR trial. Circulation. 2022;145:648-658.
6. Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2022;43:561-632.
7. Popma JJ, Deeb GM, Yakubov SJ, et al. Evolut Low Risk Trial Investigators. Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients. N Engl J Med. 2019;380:1706-1715.
8. Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low risk patients. N Engl J Med. 2019;380:1695-1705.
QUESTION: What’s your interpretation of the REVIVED BCIS2 trial? Which, would you say, are its most positive and debatable features?
ANSWER: The REVIVED BCIS21 trial randomized stable patients with ischemic dilated cardiomyopathy to undergo percutaneous coronary intervention (PCI) along with optimal medical therapy (OMT) or OMT alone without revascularization. The trial included patients with left ventricular ejection fraction ≤ 35%, extensive coronary artery disease, and viability in 4 or more segments amenable to PCI. The results proved that the 2 strategies offered comparable outcomes regarding the primary composite endpoint of all-cause mortality or hospitalization-related heart failure (37.2% vs 38.0%; hazard ratio, 0.99; 95% confidence interval, 0.78-1.27; P = .96). There were no differences in the changes in left ventricular ejection fraction recorded at 6 months and at 1 year, with improvement confirmed in both groups.2 Previously, the STICH trial2,3 had demonstrated that surgical revascularization combined with OMT provided long-term overall survival benefits in patients with ischemic dilated cardiomyopathy, despite an initial increase in surgery-related mortality. Therefore, it was believed that the REVIVED BCIS2 trial, with the lower perioperative risk associated with PCI, could equal or even exceed these benefits. However, things have changed since the publication of the STICH trial, including improvements in pharmacological therapy, greater use of devices such as implantable cardioverter-defibrillators and cardiac resynchronization therapy, closer follow-up of patients with heart failure, and widespread use of cardiac rehabilitation programs. The REVIVED BCIS2 trial proves that current OMT with the use of these resources in patients with ischemic dilated cardiomyopathy provides certain benefits regarding mortality and heart failure-related hospitalizations that are not enhanced by revascularization, at least with the percutaneous approach.
The most positive feature of this study is that it addresses an open question on the need for the systematic use of PCI in these patients and it does so with a methodologically appropriate clinical trial. The most debatable aspects are the definition of ischemic dilated cardiomyopathy and the achievement of complete revascularization. To characterize cardiomyopathy as ischemic, a BCIS-Jeopardy score4 ≥ 6 was required, with 49% of the patients having 2-vessel disease, while the median number of lesions and vessels treated per patient in the PCI group was 2, and complete revascularization was achieved in 71% of the patients.1
Q.: The STICH trial2 showed benefits beyond the 5- to 10-year mark, but in the REVIVED BCIS2 trial, the median follow-up was 3 to 4 years, although the patients’ age in the 2 studies was very different. What do you make of this?
A.: In the STICH trial, the all-cause mortality curves (primary endpoint) began to separate at the 2-year follow-up, and the original publication of the study, with a median follow-up of 4.7 years, failed to show a significant reduction in the primary endpoint. What demonstrated the prognostic benefit of cardiac surgery in addition to OMT was extending the follow-up to 10 years (median, 9.8 years).3 This reveals several points: on the one hand, the increased perioperative morbidity and mortality and, on the other hand, the long-term benefits of alleviating myocardial ischemia, leading, among other things, to lower rates of reinfarction and ventricular arrhythmias5 This is especially relevant when treating younger patients, whose lower surgical risk and longer life expectancy allow us to actually see clinical benefits. Although PCI was not associated with higher perioperative mortality in the REVIVED BCIS2 trial, there were no significant separations of the primary endpoint curves during the study.
We need to obtain data from a longer follow-up to detect any potential benefits associated with PCI. Additionally, the mean age of the REVIVED trial population was 70 years (compared with the median of 60 years in the STICH trial), making it less likely to achieve the same long-term benefits associated with surgical revascularization.
Q.: What was the clinical profile of these patients, and to what extent was their medical therapy optimized during randomization? Do you think they could have progressed to advanced stages of cardiomyopathy, and if so, could that have impacted the outcomes?
A.: The participants’ clinical profile was typical of this kind of disease. Most were men (88%), and 56% of them had a history of hypertension, 41% had diabetes, and 53% had previous myocardial infarction: 67% were angina-free, 20% had a history of previous PCI, and 5% had undergone surgical revascularization. They were in a favorable functional class (74% were in NYHA class I or II), while only 33% had been hospitalized due to heart failure in the previous 2 years, and the median N-terminal pro-brain natriuretic peptide (NT-proBNP) was 1400 pg/mL. Therefore, their baseline characteristics do not support the assumption that they were in an advanced stage of the disease.6 Although mortality during follow-up was high (32%), it was consistent with what we would expect of patients with ischemic dilated cardiomyopathy,7,8 while the rate of heart failure-related hospitalizations was relatively low (15%). Based on their clinical profile, these patients would have been eligible for improvement with percutaneous revascularization. When the participants were randomized, 89% were on an angiotensin-converting enzyme inhibitor, combined with an angiotensin II receptor antagonist or sacubitril-valsartan, 91% were on beta-blockers, and 49% were on mineralocorticoid receptor antagonists. Although this is a well-optimized regimen, there is still room for improvement, because only 5% of the participants were on sacubitril-valsartan, half of them were not on aldosterone antagonists, and sodium-glucose co-transporter-2 inhibitors were not yet considered part of the foundational treatment of heart failure. Indeed, at the 2-year follow-up, only 20% were on sacubitril-valsartan and 55% were on mineralocorticoid receptor antagonists. Additionally, a low percentage of participants (23%) had a defibrillator or a cardiac resynchronizer.1
Q.: Do you agree that the trial questions the validity of viability tests? Although a 25% cutoff value for late gadolinium enhancement was established in cardiac magnetic resonance, in cases with 25% to 50% enhancement it was left to the local investigators’ discretion to use another imaging modality, such as dobutamine echocardiography. Do you think places doubt on the criteria applied to the trial?
A.: The STICH trial viability subanalysis already cast doubt on the utility of detecting a viable myocardium through single-photon emission computed tomography or dobutamine echocardiography to predict favorable outcomes after revascularization.9 The REVIVED BCIS2 also failed to demonstrate that viability-guided revascularization is able to reduce mortality or improve cardiac remodeling. In this trial, a larger number of dysfunctional—yet viable—myocardial segments were not associated with prognosis or with the possibility of improved ventricular function, whereas less myocardial scarring did predict a more favorable prognosis and a higher likelihood of reverse remodeling. This was independent of the baseline ejection fraction and extent of coronary artery disease.10 The results should prompt us to revisit the notion of hibernating myocardium and avoid basing the coronary revascularization strategy solely on viability tests.11 In this trial, cardiac magnetic resonance was the preferred imaging modality to assess viability (used in 71% of the patients). Considering segments with a maximum late enhancement of 25% as viable was a positive aspect, because participants with higher theoretical probabilities of improving after PCI were selected. Although another additional imaging modality could be used in patients with late enhancement between 26% and 50%, in practice, only 8 patients1 received more than 1 viability test, so this does not seem to be an important point.
Q.: Considering the possibility that coronary artery disease can be concurrent with cardiomyopathy, without it necessarily being the main cause, do you think there is a specific patient profile that could benefit from PCI or, at the very least, could be worth further study?
A.: The subgroup analysis did not show any significant treatment interaction in the prespecified subgroups of interest.1 However, data from the study allow us to speculate on which participants might benefit more from PCI. The trial included few patients with limiting angina, thus making the findings less applicable to these patients. The study showed differences in favor of PCI regarding quality of life at the 6- and 12-month follow-up (becoming equal at 2 years in the 2 groups), suggesting that PCI might be crucial for patients with angina.5 Additionally, PCI-treated patients showed a trend toward fewer appropriate implantable cardioverter-defibrillator therapies,1 indicating that revascularization could be more beneficial in individuals in whom ventricular arrhythmias are an issue. Other subgroups of interest would be patients with more extensive coronary artery disease, those with complete revascularization, and those with greater ventricular dysfunction. Future publication of these patients’ outcomes could help in the decision-making process.6
Finally, while surgical revascularization should be the preferred strategy for patients with ischemic dilated cardiomyopathy,7 PCI should still play a role in the management of young patients with significant coronary artery disease and high surgical risk or poor distal beds. With the current evidence available and contemporary OMT, a clinical trial should be conducted comparing 3 therapeutic strategies: isolated OMT, OMT along with surgical revascularization, and OMT alongside PCI in patients with ischemic dilated cardiomyopathy. The selection criteria should not consist of viability but rather the feasibility of achieving complete myocardial revascularization in regions at-risk, and follow-up should be long-term.
FUNDING
None reported.
CONFLICTS OF INTEREST
None.
REFERENCES
1. Perera D, Clayton T, O'Kane PD, et al. Percutaneous revascularization for ischemic left ventricular dysfunction. N Engl J Med. 2022;387:1351-1360.
2. Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364:1607-1616.
3. Velazquez EJ, Lee KL, Jones RH, et al. Coronary-Artery Bypass Surgery in Patients with Ischemic Cardiomyopathy. N Engl J Med. 2016;374:1511-1520.
4. Morgan H, Ryan M, Briceno N, et al. Coronary Jeopardy Score Predicts Ischemic Etiology in Patients With Left Ventricular Systolic Dysfunction. J Invasive Cardiol.2022;34:E683-E685.
5. Ezad SM, Ryan M, Perera D. Can Percutaneous Coronary Intervention Revive a Failing Heart?Heart Int. 2022;16:72-74.
6. Vergallo R, Liuzzo G. The REVIVED BCIS2 trial:percutaneous coronary intervention vs. optimal medical therapy for stable patients with severe ischaemic cardiomyopathy. Eur Heart J. 2022;43:4775-4776.
7. Liga R, Colli A, Taggart DP, Boden WE, De Caterina R. Myocardial Revascularization in Patients With Ischemic Cardiomyopathy:For Whom and How. J Am Heart Assoc. 2023;12:e026943.
8. Perera D, Clayton T, Petrie MC, et al. Percutaneous Revascularization for Ischemic Ventricular Dysfunction:Rationale and Design of the REVIVED BCIS2 Trial:Percutaneous Coronary Intervention for Ischemic Cardiomyopathy. JACC Heart Fail. 2018;6:517-526.
9. Bonow RO, Maurer G, Lee KL, et al. Myocardial viability and survival in ischemic left ventricular dysfunction. N Engl J Med. 2011;364:1617-1625.
10. Perera D. Effect of Myocardial Viability, Functional Recovery and ICP on Clinical Outcomes in the REVIVED BCIS2 Trial. En:American College of Cardiology 2023 Scientific Session;2023 March 4-6;New Orleans, LA, USA. Available at: https://accanywhere.acc.org/media/c2f4157c-0bef-4d69-87b4-ac6ab6224e07. Accessed 9 Jul 2023.
11. Ryan M, Morgan H, Chiribiri A, Nagel E, Cleland J, Perera D. Myocardial viability testing:all STICHed up, or about to be REVIVED?Eur Heart J. 2022;43:118-126.RECIC_23_064
QUESTION: What is your opinion of the REVIVED BCIS2 trial? Which, would you say, are its most positive and most debatable features?
ANSWER: The REVIVED BCIS21 is a prospective, multicenter, randomized, open-label trial of stable patients with severe left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤ 35%), extensive coronary artery disease with a British Cardiovascular Intervention Society (BCIS) risk score ≥ 6, and evidence of viability in at least 4 dysfunctional segments amenable to percutaneous coronary intervention (PCI). Patients were randomized in a 1:1 ratio to receive PCI along with optimal medical therapy (OMT), or OMT alone. The OMT included pharmacological therapy and implantable devices for the management of heart failure.
The primary endpoint was a composite of all-cause mortality or hospitalization over a minimum follow-up of 24 months. Secondary endpoints included 6- and 12-month echocardiographic measurements of LVEF (core lab), quality of life measurement through questionnaires such as the Kansas City Cardiomyopathy Questionnaire, the EuroQol Group 5-Dimensions 5-Level Questionnaire, and New York Heart Association Functional Class, cardiovascular death, acute myocardial infarction (AMI), appropriate defibrillator therapy (antitachycardia pacing or shock), unplanned revascularization, brain natriuretic peptide values, functional class, and major bleeding.
A total of 700 patients were included, of which 347 were randomized to PCI and 353 to OMT. The participants’ mean age was 69 years, and 12% were women. The median follow-up was 41 months (importantly, randomization began back in 2013 and the study was published in 2022), and 40 hospitals in the United Kingdom participated in the trial. The participants received guideline-directed pharmacological therapy (93% received beta-blockers; 66% angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers, and 56% aldosterone antagonists). More than 30% of the participants in the 2 groups received a defibrillator or resynchronization device before or during the study period.
The primary endpoint was observed in 37.2% of the PCI group and 38% of those in the OMT group. LVEF was similar in the 2 groups both at 6 and 12 months. Although quality of life questionnaires favored PCI at 6 and 12 months, this improvement was attenuated at 24 months.
I believe the main strength of the study is that it is the first to compare this revascularization mode (PCI) with OMT in ischemic patients with LVEF ≤ 35%. Previously, we only had the STITCH2 trial for this patient subgroup, which compared coronary revascularization surgery with OMT in a population of younger patients with less extensive coronary artery disease. This trial did not show any benefits associated with surgery in terms of overall 5-year mortality but did show benefits at the extended 10-year follow-up. Another important point is the efficacy of OMT in these patients today; in fact, the number of events was even lower than initially anticipated by the investigators.
Regarding debatable aspects, I’d say that, although the patients were selected on the basis of myocardial viability; until now viability testing has never been used to predict the effectiveness of revascularization.2,3 And to be honest, it may not be the most suitable way to identify patients who will benefit from PCI in this population.4 Additionally, most patients were asymptomatic (66%) or showed mild angina symptoms, which could undoubtedly have impacted the results.
Q.: What was the patients’ coronary artery disease profile? What do think of the use of an angiographic risk index like the BCIS in this trial compared with alternatives like the SYNTAX score, and especially functional assessment using pressure guidewires? How far do you think the causal relationship between coronary artery disease and dilated cardiomyopathy was clear?
A.: Compared with the STITCH2 trial, the REVIVED BCIS21 trial included older patients with more extensive coronary artery disease and more contemporary medical treatment. However, the assessment of disease extent and the significance of coronary involvement according to the BCIS5 score raises some questions. In fact, it’s surprising that despite having mean scores of 10, almost half of the participants had 2-vessel disease, and the median number of vessels and lesions treated was 2,6 which raises concerns about how many lesions were not revascularized. Also, it is unclear whether there could have been some selection bias, because some participants with more extensive coronary artery disease amenable to surgery might have been referred directly and not included in the study.
On the other hand, it seems obvious that lesion assessment with pressure guidewires would have provided the study with significant reliability. If we look at the BCIS score, lesions are defined as severe when stenosis is > 70%. Especially in a population of mostly asymptomatic patients or those with mild angina symptoms and multivessel disease, it seems more than reasonable to select target lesions and vessels based on coronary physiology assessment.
Q.: What can you tell us about revascularization? Could the degree of complete revascularization or crossing over from OMT to PCI have impacted the results?
A.: As I mentioned, despite having extensive coronary artery disease according to the angiographic scale used, almost half of the participants had 2-vessel disease, and the median number of treated lesions was 2. Additionally, the authors mention that they have not yet analyzed whether the target vessels coincided with segments of affected viability, complicating interpretation of the results even more. Undoubtedly, if some lesions were left untreated while others without indications were indeed treated, the impact on the results is obvious. Also, as you mentioned in your question, unplanned revascularization was more frequent in the OMT group (10.5%) than in the PCI group (2.9%), which could explain why the PCI group showed better quality of life scores at 6 and 12 months, but not at 24 months when the impact of the higher rate of unplanned revascularizations in the OMT group may have been a factor.
Q.: Were there any benefits seen in any type of clinical event in the PCI group?
A.: Yes. The PCI group experienced fewer episodes of ventricular tachycardia or fibrillation than the OMT group, suggesting a lower ischemic burden and arrhythmic risk in the OMT group. Additionally, the number of defibrillators implanted after randomization was lower in the PCI group.
On the other hand, although the incidence of AMI was similar in the 2 groups (around 10%), almost half were perioperative in the PCI group, whereas none were perioperative in the OMT group, resulting in more spontaneous AMIs in the OMT group (9% vs 5%). This datum might be clinically relevant because the ISCHEMIA trial7 revealed that spontaneous AMIs have a worse prognosis than perioperative AMIs.
As I mentioned previously, the PCI group also benefitted in terms of quality of life at 6 and 12 months, but not at 24 months.
Q.: Bearing in mind that coronary artery disease may have a causal relationship with cardiomyopathy, do you think there is a particular patient profile that could benefit from PCI or, at the least, merit further investigation of this link?
A.: Based on the REVIVED trial results, it’s obvious that percutaneous revascularization in stable patients with severe LVEF depression, multivessel disease, and few or no angina symptoms provides little benefit. If we remember that lesion selection was purely angiographic (lesions with stenosis ≥ 70%), and that we just don’t know if the treated lesions coincided with segments of abnormal viability, patients with severe left ventricular dysfunction, angina symptoms, angiographically significant lesions, and abnormal coronary physiology assessments (or left main coronary artery intravascular ultrasound assessments)8 may constitute a group that could benefit from coronary angioplasty in terms of survival and quality of life.
FUNDING
None reported.
CONFLICTS OF INTEREST
None.
REFERENCES
1. Perera D, Clayton T, O'Kane PD, et al. Percutaneous revascularization for ischemic left ventricular dysfunction. N Engl J Med.2022;387:1351-1360.
2. Velazquez EJ, Lee KL, Jones RH, et al. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med.2016;374:1511-1520.
3. Cleland JG, Calvert M, Freemantle N, et al. The heart failure revascularisation trial (HEART). Eur J Heart Fail. 2011;13:227-233.
4. Ryan M, Morgan H, Chiribiri A, Nagel E, Cleland J, Perera D. Myocardial viability testing:all STICHed up, or about to be REVIVED?Eur Heart J. 2022;43:118-126.
5. Perera MA, Stables R, Booth J, et al. The Balloon pump-assisted Coronary Intervention Study (BCIS-1):Rationale and design. Am Heart J. 2009;158:910-916.
6. Vergallo R, Liuzzo G. The REVIVED-BCIS2 trial:percutaneous coronary intervention vs. optimal medical therapy for stable patients with severe ischaemic cardiomyopathy. Eur Heart J. 2022;43:4775-4776.
7. 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.
8. De Maria GL, Testa L, de la Torre Hernandez JM, et al. A multi-center, international, randomized, 2-year, parallel-group study to assess the superiority of IVUS-guided PCI versus qualitative angio-guided PCI in unprotected left main coronary artery (ULMCA) disease:Study protocol for OPTIMAL trial. PLoS One. 2022;17:e0260770.
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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