Article
Debate
REC Interv Cardiol. 2019;1:51-53
Debate: MitraClip. The heart failure expert perspective
A debate: MitraClip. Perspectiva del experto en insuficiencia cardiaca
aServicio de Cardiología, Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, Valencia, Spain bCIBER de Enfermedades Cardiovasculares (CIBERCV), Spain
Related content
Debate: MitraClip. The interventional cardiologist perspective
QUESTION: Do we have enough evidence to be able to say that the coronary recanalization of a chronic total coronary occlusion (CTO) improves the prognosis of patients?
ANSWER: I would say so. I believe it is hard to have well-designed, randomized clinical trials with large populations of patients and long follow-up periods on this issue comparing the 3 possible strategies of treatment (drugs, surgery, and percutaneous coronary interventions) which, by the way, are the prerequisites to show some mortality net benefit in this group of patients. Also, the results from the procedures performed in the different groups are not comparable whatsoever.
On the other hand, if we look at the registries already published and presented in congresses over the last few years (3-4 years), we will see that only those with long follow-up periods are positive. Usually, the revascularization of a CTO has no implications in the rate of infarction at follow-up, yet the overall and cardiac mortality rate of non-revascularized patients compared to revascularized patients (both percutaneously and using surgery) trebles compared to the population of patients with CTO who are on medical treatment.
The only 2 randomized clinical trials ever published that compare the clinical evolution of patients with a CTO based on the treatment received (medical vs interventional) are the EuroCTO1 and the DECISION-CTO trials.2 Unfortunately, both were interrupted before reaching the population for which they were designed due to their low patient inclusion rate. Their results are contradictory, unfavorable in the DECISION-CTO and favorable in the EuroCTO trial, but their designs are very different. In the DECISION-CTO trial, patients with multivessel disease received treatment in non-occluded vessels at the interventional cardiologist’s criterion; as a matter of fact, 50% of the patients in both groups received treatment with angioplasty of vessels without chronic occlusions. On the other hand, in the EuroCTO trial the non-occluded vessels of patients with multivessel disease were systematically revascularized and then randomized to receive medical treatment or undergo angioplasty for their CTO. Also, in the DECISION-CTO clinical trial there is a high rate of crossing between the different modalities of treatment: 3 days after randomization, 19.6% of patients form the medical treatment arm crossed to the revascularization arm vs 7.3% at 12 months in the EuroCTO trial. In the DECISION-CTO trial, at the 4-year follow-up, no differences were seen between the 2 arms in the following events: death, infarction, stroke, and revascularization (22.3% vs 22.4%; P = .86) or in the quality of life test results. Conversely, in the EuroCTO clinical trial the scores measuring the quality of life improved significantly in the invasive treatment arm, and the 12-month adverse events were similar in both arms.
Q.: In what subgroups of patients or situations should we expect to see greater prognostic benefits?
A.: We should focus on higher risk populations that are probably under-represented here.
Diabetics with CTO have a higher incidence of multivessel disease, more calcified blood vessels, and more risk factors compared to non-diabetic patients. Insulin-dependent diabetic patients with renal failure are the subpopulation with the most somber prognosis of all. In all the clinical trials conducted so far, the success rate of the angioplasty in the management of CTO is lower than that of non-diabetic patients. Also, to this day, from the prognostic point of view, surgery is superior to angioplasty, meaning that we should probably be very cautious when indicating an angioplasty for a CTO in these patients.
The subgroup of elderly patients (≥ 75 years) is a particularly frail population with worse left ventricular ejection fraction (LVEF), worse renal function, and a higher incidence of multivessel disease and left main coronary artery disease compared to patients < 75 years. The oldest patients are revascularized less frequently and with a lower success rate, but procedural complications are similar to the ones we find in younger patients. When selecting our patients, we should take into consideration that the age, creatinine, and ejection fraction (ACEF) score, high SYNTAX scores, and damage to the left main coronary artery are prognostic factors that we should take into consideration in this population of patients regardless of short-term mortality. We should not forget that, at the 4-year follow-up, the mortality rate of patients ≥ 75 years with CTO doubles that of patients < 75 years with CTO and that, in non-revascularized elderly patients, mortality doubles compared to revascularized patients. So maybe we should take a different approach towards this often-under-represented population.
Even though women with CTO have a higher incidence of risk factors compared to men with CTO and even though they amount to 15% of the studies population, the rates of success and complications between sexes are similar.
Another especially sensitive group is that of patients with CTO and a low LVEF. The angioplasty of the CTO is not accompanied by higher rates of complications or lower rates of success, and the improved prognosis is obvious because even though it is indicated it has proven to improve the LVEF.
Q.: And regarding symptom and functional improvement?
A.: The answer is affirmative in both cases. The studies conducted so far using magnetic resonance imaging allow us to say that the revascularization of a CTO in patients with preserved LVEF is accompanied by significant reductions in the amount of ischemic segments and the corresponding improvement of segmental contractility. There is a positive remodeling of the left ventricle with reduced end-diastolic volume. Also, if the necrotic mass is compared at baseline and at 6 months, we will see that it does not grow any bigger, which shows how safe the procedure of revascularization really is.
If we focus on the most fragile patients of all with the highest possible benefits such as patients with CTO and a LVEF < 40%, the results are more noticeable. Our group published the results of the 6-month follow-up of a group of 29 patients in whom we also found less ischemic segments, better contractility, and a 6 percentage-point improved LVEF (31.3% ± 7.4% vs 37.7 ± 8; P < .001) with significant functional repercussion, reduced brain natriuretic peptide levels (323 ± 657 pg/mL [95% confidence interval (95%CI), 60.4-238.2] vs 123 ± 151 pg/dL [95%CI, 40.6 ± 154.5]; P = .004), improved heart failure functional classification (New York Heart Association baseline functional class I and II: 72% vs 100%; P = .004), and improved angina pectoris (34.4% in baseline situation vs 3.1% at follow-up; P = .002).3
The greatest contribution of the EuroCTO trial after the 12-month follow-up is showing that there is a significant improvement in the scores used to measure quality of life (Seattle Angina Questionnaire) with a lower frequency of angina (5.23; 95%CI, 1.75-8.71; P = .003), better quality of life (6.62; 95%CI, 1.78-11.46; P = .007), fewer limitations to do physical activity (81.1; 95%CI, 77.6-100 with angioplasty vs 75.9; 95%CI, 71.3-80.5 with medical treatment; P = .02), and a larger number of patients completely asymptomatic in the group treated with angioplasty compared to the group that received medical treatment (71.6% vs 5.8%; P = .008).
Q.: What clinical indications does the percutaneous revascularization of a CTO have?
A.: If we follow the recommendations established by the European Society of Cardiology,4 the revascularization of CTO has a grade IIa indication with a B-level of evidence as long as patients have medical treatment-resistant angina or a well-documented wide ischemic region. As far as I know, these recommendations are not consistent with the routine daily practice.
The requirements to revascularize a CTO should be the same as for the revascularization of significant stenosis, that is, confirmed ischemia, current feasibility, and symptoms. However, regarding the symptoms, at least in my own experience, most patients with CTO also have anginal equivalents, and often complain that they get tired easily and unjustifiably for their age or LVEF; and when they have progressive angina pectoris, most of the times it is due to a developing stenosis in the donor vessel of collateral circulation.
We know that if the underlying myocardium is viable, a CTO behaves functionally like a 99% stenosis. So, I believe that the revascularization of CTO should have the same indications as the revascularization of any other lesion, as long as the procedure is performed with guarantees and by experienced interventional cardiologists.
Q.: What practical recommendations can you share with us to approach the interventional management of CTO with higher levels of success?
A.: The field of CTO is really something special because it requires not only particular skills but also a special attitude. In my personal opinion, all interventional cardiologists who want to deal with CTO should have 2 basic characteristics: patience and perseverance.
Perseverance is key because, even if we are pretty good interventional cardiologists for all other types of lesions, the management of CTO requires a very specific and prolonged learning curve, estimated at around 50 annual cases for a minimum of 3 years to be able to reach an acceptable rate of success. Therefore, it is advisable that not all interventional cardiologists of the same center specialize in the management of CTO because nobody would reach the level of expertise required. A reasonable idea would be to estimate the number of interventional cardiologists based on the number of actual patients who would be treated based on the volume of cases handled by each center.
One can never stress enough something so simple as preparing the cases properly. It is essential to have deep knowledge of the coronary anatomy, that is, carry out a careful frame-by-frame review of the diagnostic coronary angiography to be able to characterize the plaque and the collaterals. Also, it is imperative to think of the material and the possible techniques that will be used. Added to the coronary anatomy, we also need good in-depth information on the patient, in particular his renal function, risk of bleeding, therapeutic adherence, capacity of collaboration, osteoarticular situation, and frailty.
We also consider the possibility of asking for help from other colleagues more experienced than us both at the beginning of the activity, and in second attempts in patients in whom we have already failed.
Another important issue is the material we plan to use because this is a field in continuous evolution. Although it is not possible to know every piece of equipment currently available, once we have made our choice, we need to know its characteristics, how it has been built, what it is designed to do, and how it should be used. Ongoing training is also important, so periodically attending specialized congresses are a good resource if we want to keep up to date.
It is essential to guarantee the patient’s safety; we should not forget that success means achieving TIMI (Thrombolysis in Myocardial Infarction) grade III flow without significant residual stenosis, loss of branches (a prognostic factor already confirmed long ago) and without any associated complications. The implementation of simple resources within our routine cath lab practice may help; here are a few examples: stop the procedure if losing collateral circulation and resume it if we think we can introduce some changes in the technique that we still have not used or have used incorrectly; ask the heart team to signal us whenever we have passed 3.7 times the volume of contrast administered in relation to the patient’s creatinine clearance levels to avoid contrast-induced nephropathy; and avoid high doses of radiation by asking the heart team to signal whenever we have reached the 3 Gy mark, and consider stopping the procedure whenever we come close to the 5 Gy mark if we have not made very significant advances, basically if we have not crossed the lesion with the guidewire.
CONFLICTS OF INTEREST
V. Martin-Yuste declared no conflicts of interest whatsoever regarding the writing of this manuscript.
REFERENCES
1. Werner GS, Martin-Yuste V, Hildick-Smith D, et al. A randomized multicentre trial to compare revascularization with optimal medical therapy for the treatment of chronic total coronary occlusions. Eur Heart J. 2018;39:2484-2493.
2. Lee SW, Lee PH, Ahn JM, et al. Randomized Trial Evaluating Percutaneous Coronary Intervention for the Treatment of Chronic Total Occlusion. Circulation. 2019;139:1674-1683.
3. Cardona M, Martín V, Prat-Gonzalez S, et al. Benefits of chronic total coronary occlusion percutaneous intervention in patients with heart failure and reduced ejection fraction:insights from a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson. 2016;18:78.
4. Neumann F-J, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019;40:87-165.
QUESTION: Is there enough evidence to be able to say that the coronary recanalization of a chronic total coronary occlusion (CTO) improves the prognosis of patients?
ANSWER: No, there is not. However, many cardiologists believe so based on observational studies that report that patients with CTO who are successfully treated have better prognosis compared to those who undergo failed procedures.1 In many of these registries, the baseline characteristics, risk factors, ventricular function, and coronary anatomy are substantially different between patients treated successfully and those treated with failed procedures.2,3 When the outcomes are adjusted by these confounding variables, success in treatment does not condition the prognosis anymore.4
One less biased way to know the effect this has on the prognosis of patients undergoing percutaneous treatment of their CTO is to compare them to those who receive medical treatment. In this sense, several registries have been published with different results. For instance, in a study of patients with CTO treated percutaneously versus patients treated medically (using propensity-score matching), Ladwiniec et al.,5 showed a lower rate for the composite endpoint of death or myocardial infarction at 5 years, but not death as the single event that was favorable to those patients treated percutaneously. However, Yang et al.,6 with a similar matching of patients, did not show any benefits derived from treating the CTO. This shows that dozens of registries on CTO still cannot replace the need for randomized clinical trials.7,8
Very few studies randomizing patients to having their CTO treated or not have been published so far, and not all of them have had the assessment of cardiovascular events as their primary endpoint. The EXPLORE trial included 304 patients with a CTO as the non-culprit artery in individuals with ST-segment elevation myocardial infarction treated with primary angioplasty.9 At 4 months no differences were seen in the ejection fraction, the left ventricular end-diastolic volume (the primary endpoint) or cardiovascular events analyzed through cardiovascular magnetic resonance. By the way, the result of this study had somehow already been anticipated in a Spanish registry.10 The REVASC clinical trial randomized 205 patients with stable chronic coronary artery disease to treat or not to treat a CTO.11 At 6 months, no differences were seen in the global or segmental left ventricular function (the primary endpoint) or cardiovascular events analyzed through cardiovascular magnetic resonance between the 2 groups. The EuroCTO trial ranzomized 396 patients (2:1) to treat or not to treat a CTO.12 At the 12-month follow-up, no differences were seen in the rate of cardiovascular or cerebrovascular events reported in the arm where the CTO was treated. It should be mentioned that this study anticipated including 1200 patients but had to be interrupted prematurely due to its low inclusion rate. The IMPACTOR-CTO clinical trial randomized 96 patients with a CTO in their right coronary artery to receive percutaneous treatment or not.13 This study conducted in a single Russian center showed a reduction of ischemia and improved 6-minute walk test results without any changes in cardiovascular events.
Finally, the DECISION-CTO clinical trial has been the most important study published so far with 834 randomized patients.14 During a mean 4-year follow-up, the incidence of the composite endpoint of death, myocardial infarction or stroke was similar in both arms.
Therefore, to this day no randomized clinical trial or meta-analysis of all randomized clinical trials15 published so far has been able to prove that treating a CTO changes the prognosis of patients.
Q.: In what subgroups of patients or situations should we expect to see greater prognostic benefits?
A.: There is something clear: the CTO is a common lesion in patients with ischemic heart disease16 and its presence is associated with poor prognosis.17 Therefore, the issue is to be able to identify those patients whose prognosis may change with a percutaneous coronary intervention. The revascularization of a CTO that causes significant ischemia (> 10% quantified using imaging modalities) may improve long-term prognosis as a clinical trial is trying to prove: the ISCHEMIA-CTO (Nordic and Spanish Randomized Trial on the Effect of Revascularization or Optimal Medical Therapy in Chronic Total Coronary Occlusions with Myocardial Ischemia; NCT03563417). But before the ISCHEMIA- CTO findings become available, we will probably have the results of the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches, NCT01471522) clinical trial first. This study has been trying to prove something similar in patients who do not necessarily have a CTO. If the ISCHEMIA trial is positive, the hypothesis of revascularizing a CTO based on the presence of significant myocardial ischemia will be much more attractive.
Q.: And what about symptom and functional improvement?
A.: There are at least 2 studies that indicate that symptomatic patients can improve once their CTO has been treated. The FACTOR is a non-randomized clinical trial that showed improved quality of life test results in symptomatic patients.18 This is a small study of 125 non-randomized patients in whom the quality of life test is analyzed 1 month after the procedure. Also, it compares patients successfully treated versus patients with failed procedures. The benefit derived from successful treatment was greater in symptomatic patients and significant with respect to physical activity and quality of life according to the Seattle Angina Questionnaire. However, the most significant evidence of symptom improvement after treating a CTO comes from the EuroCTO clinical trial that showed modest symptomatic benefits in the quality of life test results after percutaneous treatment.12 However, the premature interruption of the study and its low inclusion rate make the results questionable.
Regarding functional improvement, there is also evidence that the treatment of a CTO modestly reduces the ischemic region in patients with at least mild to moderate ischemia19 and barely improves ventricular function,20 although we still do not know how these aspects may impact the patient’s clinical signs.
Q.: What clinical indications does the percutaneous revascularization of a CTO have?
A.: Today, the main indication for treating a CTO should be to improve symptoms in patients who remain symptomatic despite the optimal medical treatment.19 In order to achieve this, the occluded artery needs to be recanalized effectively, which totally depends on its angiographic characteristics and the experience of the interventional cardiologist in charge.
The current clinical guidelines of the European Society of Cardiology contemplate 1 indication only for the management of a CTO: patients with angina refractory to treatment and a significant ischemic region as seen on the imaging modalities.21 This is a class IIa indication with a B-level of evidence. As long as we don’t have any other evidence, we encourage all Spanish interventional cardiologists experienced in the management of CTO, who are actually many and with very good results,22 to include patients in the current ISCHEMIA-CTO randomized clinical trial. This clinical trial is essential and will shed light on many of the issues we have discussed here.
CONFLICTS OF INTEREST
None declared.
REFERENCES
1. Pancholy SB, Boruah P, Ahmed I, Kwan T, Patel TM, Saito S. Meta-Analysis of Effect on Mortality of Percutaneous Recanalization of Coronary Chronic Total Occlusions Using a Stent-Based Strategy. Am J Cardiol. 2013;111:521-525.
2. Mehran R, Claessen BE, Godino C, et al. Long-term outcome of percutaneous coronary intervention for chronic total occlusions. JACC Cardiovasc Interv. 2011;4:952-961.
3. BardajíA. Chronic total occlusion:To treat or not to treat. World J Cardiol. 2014;6:621-629.
4. Yamamoto E, Natsuaki M, Morimoto T, et al. Long-term outcomes after percutaneous coronary intervention for chronic total occlusion (from the CREDO-Kyoto registry cohort-2). Am J Cardiol. 2013;112:767-774.
5. Ladwiniec A, Allgar V, Thackray S, Alamgir F, Hoye A. Medical therapy, percutaneous coronary intervention and prognosis in patients with chronic total occlusions. Heart. 2015;101:1907-1914.
6. Yang JH, Kim BS, Jang WJ, Ahn J, Park TK, Song YB, et al. Optimal Medical Therapy vs. Percutaneous Coronary Intervention for Patients With Coronary Chronic Total Occlusion –A Propensity-Matched Analysis. Circ J. 2015;80:211-217.
7. Di Mario C, Sorini Dini C, Werner GS. Thousand Registries Are Not Worth a Randomized Trial. JACC Cardiovasc Interv. 2017;10:1535-1537.
8. BardajíA, Bonet G. Chronic total occlusion:No more meta-analysis, please –a randomized clinical trial is urgently needed. J Thorac Dis. 2015;7:E219-E221.
9. Henriques JP, Hoebers LP, Råmunddal T, et al. Percutaneous Intervention for Concurrent Chronic Total Occlusions in Patients With STEMI:The EXPLORE Trial. J Am Coll Cardiol. 2016;68:1622-1632.
10. Ariza-Sole A, Teruel L, di Marco A, et al. Prognostic Impact of Chronic Total Occlusion in a Nonculprit Artery in Patients With Acute Myocardial Infarction Undergoing Primary Angioplasty. Rev Esp Cardiol. 2014;67:359-366.
11. Mashayekhi K, Nührenberg TG, Toma A, et al. A Randomized Trial to Assess Regional Left Ventricular Function After Stent Implantation in Chronic Total Occlusion:The REVASC Trial. JACC Cardiovasc Interv. 2018;11:1982-1991.
12. Werner GS, Martin-Yuste V, Hildick-Smith D, et al. A randomized multicentre trial to compare revascularization with optimal medical therapy for the treatment of chronic total coronary occlusions. Eur Heart J. 2018;39:2484-2493.
13. Obedinskiy AA, Kretov EI, Boukhris M, et al. The IMPACTOR-CTO Trial. JACC Cardiovasc Interv. 2018;11:1309-1311.
14. Lee S-W, Lee PH, Ahn JM, et al. Randomized Trial Evaluating Percutaneous Coronary Intervention for the Treatment of Chronic Total Occlusion:The DECISION-CTO Trial. Circulation. 2019;139:1674-1683.
15. Barbarawi M, Kheiri B, Zayed Y, et al. Meta-analysis of Percutaneous Coronary Intervention Versus Medical Therapy in the Treatment of Coronary Chronic Total Occlusion. Am J Cardiol. 2019;123:2060-2062.
16. Råmunddal T, Hoebers L, S Henriques JP, et al. Chronic Total Occlusions in Sweden –A Report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). PLoS One. 2014;9:103850.
17. Råmunddal T, Hoebers LP, Henriques JPS, et al. Prognostic Impact of Chronic Total Occlusions. JACC Cardiovasc Interv. 2016;9:1535-1544.
18. Grantham JA, Jones PG, Cannon L, Spertus JA. Quantifying the Early Health Status Benefits of Successful Chronic Total Occlusion Recanalization:Results from the FlowCardia's Approach to Chronic Total Occlusion Recanalization (FACTOR) Trial. Circ Cardiovasc Qual Outcomes. 2010;3:284-290.
19. Hirai T, Grantham JA, Sapontis J, et al. Quality of Life Changes After Chronic Total Occlusion Angioplasty in Patients With Baseline Refractory Angina. Circ Cardiovasc Interv. 2019;12:1-8.
20. Stuijfzand WJ, Biesbroek PS, Raijmakers PG, et al. Effects of successful percutaneous coronary intervention of chronic total occlusions on myocardial perfusion and left ventricular function. EuroIntervention. 2017;13:345-354.
21. Neumann F-J, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019;40:87-165.
22. Amat-Santos IJ, Martin-Yuste V, Fernández-Díaz JA, et al. Procedural, Functional and Prognostic Outcomes Following Recanalization of Coronary Chronic Total Occlusions. Results of the Iberian Registry. Rev Esp Cardiol. 2019;72:373-382.
QUESTION: After the negative results of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) study, what new studies are dealing with renal denervation (RD) as a possible therapeutic option?
ANSWER: The results of the SYMPLICITY HTN-3 study1 were totally unexpected, particularly because those of us who had some sort of experience with this technique had lived a completely dif-ferent reality. The limitations of the study have to do with the arguable selection of patients (with non-optimized pharmacological treatment that was adjusted during follow-up and generated an unexpectedly positive response in the control group), the operators’ lack of experience (most of them conducted their first procedures within the study), and the lack of knowledge on how to conduct this procedure in order to optimize the results.
After the detailed analysis of the SYMPLICITY HTN-3 study,1 two different studies were designed with an improved device to conduct the procedure and their results have recently been made public.
The first study, the SPYRAL HTN-OFF MED2 was a randomized sham-controlled clinical trial (with a sham control group) as the proof-of-concept on the efficacy of RD to reduce arterial blood pressure (BP) in patients without concomitant pharmacological treatment. Patients with mild-to-moderate arterial hypertension (HT) (office systolic BP 150 mmHg to 180 mmHg and diastolic BP > 90 mmHg, and 24-hour ambulatory systolic BP 140 mmHg to 170 mmHg) were included in the study. Patients did not receive any prior treatment or had been without any pharmacological treatment for 3 to 4 weeks. The protocol included a drug screening of serum and plasma to confirm the absence of drugs. Patients were randomized on a 1:1 basis to RD using the multi-electrode radiofrequency catheter designed by Symplicity Spyral (Medtronic Inc., Minneapolis, United States) (n = 38) or to sham control (n = 42). The primary endpoint included changes in the 24-hour ambulatory BP, much more sensitive and specific to detect changes in the BP that measuring BP at the doctor’s office. The analysis of the first 80 patients showed a significant reduction of the 24-hour ambulatory systolic BP and office systolic BP at 3 months in favor of RD. We should mention here that during follow-up no relevant adverse events were reported in any of the two treatment arms and, as former studies had already shown, the procedure turned out to be safe and had an extremely low rate of complications.1
The endpoint of the second study, the SPYRAL HTN-ON MED,3 was to assess the efficacy of RD in a different context. The study population were not patients with resistant HT or HT naïve to drug therapy but non-severe hypertensive patients on drug therapy. Same as it happened with the SPYRAL HTN-OFF MED2 study, the primary endpoint included changes in the 24-hour BP instead of office-recorded BP changes. The patients included in the study had mild-to-moderate HT (office systolic BP between ≥ 150 mmHg and < 180 mmHg, office diastolic BP ≥ 90 mmHg, and 24-hour ambulatory systolic BP between 140 mmHg and 170 mmHg). RD reduced the 24-hour ambulatory systolic BP and the office systolic BP at 6-month follow up compared to the control arm.2
Also, a third study with a totally different device based on ultrasounds and not radiofrequency, the RADIANCE-HTN SOLO,4 confirmed the good results shown by the SPYRAL HTN-OFF MED2 in patients with moderate untreated HT with similar results in the monitoring of BP figures at follow-up, which reinforces the idea of RD for the management of HT.
Q.: What kind of technical advances have led to these positive results and what are the limitations of this kind of therapy?
A.: The critical analysis of the results shown by the SYMPLICITY HTN-31 taught us how to improve the results obtained with this procedure. It confirmed that the patients’ response was significantly better when the four quadrants of the renal artery were treated. Also, further studies showed that RD was more effective not only when the main stem of the renal artery was treated but also when the secondary branches were treated as well. A look at the anatomy of the sympathetic innervation revealed that although there were more nervous fibers at a proximal level (where treatment was formerly recommended), these fibers were at a distance from the vascular lumen that made it difficult for the radiofrequency energy released inside the blood vessel to actually reach them. On the contrary, at the most distal portion, nervous fibers are closer to the lumen and they are affected by the radiofrequency lesion. Finally, the number of radiofrequency applications somehow had something to do with efficacy in such a way that today it is adviseable to perform the maximum number of applications.
In order to simplify the procedure and taking all these premises into consideration, a new RD catheter was developed, the Symplicity Spyral, whose main characteristics with respect to the Symplicity Flex catheter (Medtronic Inc., Minneapolis, United States) with which the SYMPLICITY HTN-31 study was conducted were that it was a tetrapolar catheter (compared to the former one that was monopolar) meaning that up to 4 simultaneous radiofrequency applications could be performed; also, it cut down the duration of the application from 120 to 60 seconds. Also, the spiral-shaped catheter allowed the radiofrequency application to cover the 4 quadrants of the renal artery. Finally, the optimized caliber of the new device facilitated treating arteries of up to 3 mm in diameter vs 4 mm with the former device.
Q.: What would the actual indications of this technique be, if any?
A.: The clinical practice guidelines established by the European Society of Cardiology and the European Society of Hypertension that have been published recently5 are older compared to the knowledge acquired from the last studies we mentioned before. In these clinical guidelines, recommendations were based on the SYMPLICITY HTN-31 and its use was recommended in the setting of clinical trials only and outside the routine clinical practice.
The results of the new studies consistently show that RD is effective when it comes to improving the monitoring of the BP. Similarly, different observational registries have shown significant improvements in a large number of patients with resistant HT. In Spain we conducted a registry6 that included 125 of these patients and saw a good response in over 80% of these patients, not only when it comes to the office BP but also, and most important, when it comes to monitoring ambulatory BP. Also, RD significantly reduced pharmacological treatment, a finding that opens the door to future studies. With the evidence available today, in my opinion, patients with maintained non-monitored HT on multi-drug therapy, including aldosterone antagonists, can benefit from this procedure. We know that a reduction of 20 mmHg in systolic BP or 10 mmHg in diastolic BP cuts in half mortality risk due to cardiovascular causes. This improvement is not difficult to achieve in many of these patients after RD.
On the other hand, there are many gaps of knowledge still to be filled in in the field of RD. It is essential to identify those patients who may respond better to this procedure since the pathophysiology of HT is complex and is not always due to alterations in the regulation of the sympathetic nervous system. With regard to the procedure itself, the lack of markers to determine whether RD has been successful or not puts us on a holding pattern to see how the BP figures have evolved before determining its efficacy. The development of a non-invasive test to obtain this information should be the goal of future research. Also, the arrival of new technologies to perform RD procedures requires assessing its safety and efficacy profile in the long run.
Q.: What studies do we need so that clinical practice guidelines can recommend RD as a therapeutic alternative for the management of HT?
A.: Yet despite the raising awareness on the risks of HT and the development of new and better drugs over the last 70 years, data from 2010 in developed countries showed that one third of those who had the disease did not know about it, a little over half of them received pharmacological treatment, and less than a third had an adequate blood pressure monitoring. In this sense, the road ahead of us is a long one.
With the new Symplicity Spyral catheter the long-term safety profile is an issue we should take into consideration to give more robust guarantees that the treatment algorithm—substantially more aggressive than the algorithm used in the SIMPLICITY studies—does not cause complications.
The number of patients included in the studies is not large enough to give us evidence that the reduced BP levels observed after RD actually reduce the rate of cardiovascular events at follow-up. Improving BP is but a surrogate primary endpoint, although it is accepted that there is a correlation between lower BP levels and less cardiovascular events. Also, similar BP reductions to the ones obtained in these studies led to less events in pharmacological studies. A study that showed clinical benefits beyond the monitoring of BP would actually be conclusive in this context. Unfortunately, the high number of patients who should be included in this study probably makes such a study unfeasible. However, we should not forget that damage caused by sympathetic hyperactivity goes beyond hypertension itself and is cause for the worse glucose metabolism seen in diabetic patients, the arterial stiffness of atherosclerosis, the poor prognosis of heart failure and the impaired renal function seen in renal failure, to mention but a few.
The SPYRAL HTN-OFF MED2 and RADIANCE SOLO4 clinical trials have given us the first evidence, in a consistent way, on the possible clinical utility of RD for the management of hypertensive patients who may wish, or not, to use antihypertensive drugs. These preliminary results should be confirmed by the ongoing fundamental studies that intend to include a much larger number of patients. The pharmacological treatment of HT is a long-term option and, in most cases, for life. Even though drugs are usually well-tolerated, the noncompliance to pharmacological treatment is a common problem to the extent that almost one third of all hypertensive patients do not start a new prescription of antihypertensive medication and 50% of them become noncompliant during the first year after starting their antihypertensive medication.
In my opinion, should these results be confirmed, there will be a change of paradigm in the management of hypertension. Also, we will have to take every patient’s individual preference (shared decision-making process) into consideration on whether to follow pharmacological treatment for life or undergo a more individualized therapeutic approach through a catheter-based invasive procedure that has proven safe and with an active effect at all time.
Finally, in light of the preliminary results seen in other conditions, it will be essential to see if there is an added benefit to regulating the activity of the sympathetic nervous system beyond reducing the BP in other diseases where there is an increased sympathetic nervous system activation such as within cardiology, atrial fibrillation, and heart failure.
CONFLICTS OF INTEREST
None declared.
REFERENCES
1. Bhatt DL, Kandzari DE, O'Neill WW, et al. A Controlled Trial of Renal Denervation for Resistant Hypertension. N Engl J Med. 2014;370:1393-1401.
2. Townsend RR, Mahfoud F, Kandzari DE, et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017;390:2160-2170.
3. Kandzari DE, Böhm M, Mahfoud F, et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet. 2018;391:2346-2355.
4. Azizi M, Schmieder RE, Mahfoud F, et al. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet. 2018;391:2335-2345.
5. Williams B, Mancia G, Spiering W, et al. 2018 Practice Guidelines for the management of arterial hypertension of the European Society of Hypertension and the European Society of Cardiology: ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens. 2018;36:2284-2309.
6. Rodríguez-Leor O, Segura J, García Donaire JA, et al. Renal denervation for resistant hypertension treatment in Spain. Flex-Spyral registry. Rev Esp Cardiol. 2019. https://doi.org/10.1016/j.recesp.2019.05.013.
QUESTION: After the negative results of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) study, what new studies support renal denervation (RD) as a possible therapeutic option?
ANSWER: The introduction of RD as a therapeutic approach in patients with resistant arterial hypertension (RAHT) was very well received due to the difficulties in adequately reducing arterial blood pressure (BP) levels and, consequently, the cardiovascular and renal risk associated with the persistence of high BP. Also, this technique was backed by the extensive knowledge of the role renal sympathetic nerves play regulating BP. Some non-randomized studies revealed the virtues of this technique with significant reductions of BP levels. However, the first double-blind comparative study conducted, the SYMPLICITY HTN-3,1 did not confirm the superiority of RD over the pharmacological treatment of RAHT. This study showed that the response to RD had been lower in African-Americans and patients who had received anti-aldosterone drugs as antihypertensive therapy. The study was then heavily criticized because of the procedures used, the reduced number of ablations performed, the scarce experience of participant centers, etc.
After this first failure, several studies were designed, both in patients with and without RAHT to determine the capacity of RD to reduce the BP levels. The reason for this change can be found in the very nature of RAHT itself, the huge heterogeneity of patients, and the variability of BP values themselves. Among the studies in patients with RAHT, the DENER-HTN study (Renal Denervation in Patients With Resistant Hypertension)2 showed that RD was better compared to step-care treatment with antihypertensive drugs, although the degree of BP reduction may be biased because baseline values were much higher in the intervention group versus the control group. Among the studies in patients with no RAHT, the SPYRAL HTN-OFF MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications)3 focused on patients without prior antihypertensive therapy and naïve to treatment during the study. The SPYRAL HTN-ON MED study (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension on Standard Medical Therapy)4 included patients on antihypertensive treatment with 1 to 3 drugs and the RADIANCE-HTN SOLO5 study included controlled or non-controlled patients with low cardiovascular risk and on medication with 0 or up to 2 antihypertensive drugs. Whereas in the former, the antihypertensive treatment was kept, in the latter it was withdrawn. These studies confirmed reductions between 5 mm Hg and 7.4 mmHg in ambulatory systolic BP.6
Q.: What kind of technical advances have led to these positive results and what are the limitations of this kind of therapy?
A.: Together with the type of patients who are deemed eligible to receive RD, research has been made to develop devices capable of improving the ablation capabilities of the sympathetic nervous system and additional anatomical regions have been considered eligible for these ablations. Nonetheless, the number of ablations required has been controversial and there is no clear consensus on the different protocols used.
The new systems available today offer the possibility to act upon larger territories with every ablation by placing the electrodes around the spiral catheter and other changes in the design.
Other controversial aspects relate to what anatomical sections of the renal arteries should these ablations be performed on or what is the necessary number of ablations to be performed to achieve significant reductions in the renal sympathetic activity. Sympathetic fibers penetrate the kidney through the walls of the main renal arteries, and it is precisely on this location where these ablations were initially performed. The introduction of protocols to perform ablations in the distal branches of the renal arteries seems to achieve a greater sympathetic block and, consequently, higher effectiveness. Currently, studies should include the segments of renal arteries on which the ablations should be performed, and indicate how many of them are required, although there is not such a thing as a standard recommendation yet.
Q.: What would the current indications for this technique be, if any?
A.: The current indications for RD use are also controversial. The first possible indication would be for patients with true RAHT in whom the right pharmacological treatment cannot keep BP under control and below 140/90 mmHg.
Drug-resistance is due to several causes, many of which can be detected and fixed. An easy protocol on this regard should include: a) checking high BP levels using outpatient measures, such as home or 24-hour ambulatory monitoring; b) anamnesis aimed at detecting compliance and adherence to pharmacological treatment; c) evaluating excessive salt and alcohol intake, weight gain in cases of obesity, and use of medication or drugs that may elevate BP levels; d) excluding the presence of sleep apnea; e) assessing the need to rule out secondary arterial hypertension requiring specific treatment; and f) administering a combination of the right drugs at the right doses, especially in the case of diuretic treatment.
When this protocol is implemented, the percentage of patients diagnosed with uncontrollable RAHT does not exceed 10% and it is precisely those patients who may be eligible for RD. However, the various aspects that are still controversial today led the European Society of Cardiology and the European Society of Hypertension to avoid recommending RD outside research protocols in their latest clinical practice guidelines.7
The off-label use of RD for the management of RAHT is still far from being recommended. There is no objective reason to perform RD in situations where the right medication achieves the therapeutic goals suggested by the clinical practice guidelines.
Q.: What studies do we need so that clinical practice guidelines can recommend RD as a therapeutic alternative for the management of AHT?
A.: The development of RD technique still has a long way to go in the near future since we are still unaware of key aspects regarding its effectiveness, safety profile or who are the best candidates for this procedure.
First of all, when performing an ablation it is not possible to know when the denervation is effective enough. Until know we have tried to identify markers capable of determining whether the ablations performed were effective in suppressing adrenergic activity, because the changes in the BP levels that take place during the procedure are not associated with the degree of denervation.Therefore, the procedure is performed in the blind, with no control, and without being able to predict whether it will be successful or not. Also, it is impossible to bring procedural time down to the minimum possible with guaranteed success.
In part connected to this limitation, there is also the number of radiofrequency applications required for this procedure. Since the repetition of these may have long-term repercussions, the ideal number would be the minimum necessary to achieve the denervation we are aiming at, but, as before, it is not possible to ascertain its effectiveness during the procedure.
Similarly, to this day we still do not know the duration of the antihypertensive effect. It is well-known that after cutting the sympathetic nerves, they have the capability of reinnervation as it has been confirmed in post-transplant patients. The duration of the response, if any, is not well-known, and there are no records on its effectiveness beyond 2 or 3 years of follow-up. Although the persistence of the effect can be anticipated, it is difficult to verify because of the very nature of RAHT, as we have already seen and because this persistence is influenced by several factors related to the hypertensive state.
Also, it is important to mention the great variability in patient’s individual response to ablation. The clinical characteristics of patients who may respond better to RD are still to be established; we only have evidence that patients with isolated systolic hypertension or patients with high pulse wave velocity fare worse with RD, maybe because they have an important component of impaired vascular elasticity. Similarly, patients with a good response to anti-aldosterone drugs would also have attenuated responses since the high BP levels seen in these patients are volume-dependant. Apart from these exceptions, there are no validated markers available of a better antihypertensive response to RD.
A key element of which there is still no evidence is whether RD is better than pharmacological treatment in reducing the incidence of cardiovascular and renal events. Several studies have analyzed the reduction of organ damage, especially in left ventricular hypertrophy, and the improvement of vascular elasticity following RD, but there is no evidence that the impact RD has on morbimortality is higher compared to the one achieved with drug-induced control of the BP levels.
Last but not least, it is important to know what the possible long-term consequences of ablation may be on the renal arteries and, consequently, on renal function. The data available today tells us that in the short term there is no high risk of damage to the renal arteries, but there is no long-term data on the possible side effects.
All these questions will need to be answered in the future if renal denervation hopes to have a prominent place in the management of RAHT.8
CONFLICTS OF INTEREST
None declared.
REFERENCES
1. Bhatt DL, Kandzari DE, O'Neill WW, et al. A Controlled Trial of Renal Denervation for Resistant Hypertension. N Engl J Med. 2014;370:1393-1401.
2. Azizi M, Sapoval, M, Gosse P, et al. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial. Lancet. 2015;385:1957-1965.
3. Townsend RR, Mahfoud F, Kandzari DE, et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED):a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017;390:2160-2170.
4. Kandzari DE, Böhm M, Mahfoud F, et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs:6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet. 2018;391:2346-2355.
5. Azizi M, Schmieder RE, Mahfoud F, et al. Six-Month Results of Treatment- Blinded Medication Titration for Hypertension Control Following Randomization to Endovascular Ultrasound Renal Denervation or a Sham Procedure in the RADIANCE-HTN SOLO Trial. Circulation. 2019. https://doi.org/10.1161/CIRCULATIONAHA.119.040451.
6. Mahfoud F, Schlaich M, Böhm M, Esler M, Lüscher TF. Catheter-based renal denervation: the next chapter begins. Eur Heart J. 2018;39:4144-4149.
7. Williams B, Mancia G, Spiering W, et al. 2018 Practice Guidelines for the management of arterial hypertension of the European Society of Hypertension and the European Society of Cardiology:ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens. 2018;36:2284-2309.
8. Moss JG, Belli AM, Coca A, et al. Executive summary of the joint position paper on renal denervation of the Cardiovascular and Interventional Radiological Society of Europe and the European Society of Hypertension. J Hypertens. 2016;34:2303-2304.
QUESTION: There is no doubt that the most significant advances made back in 2018 in interventional cardiology were the longawaited results from clinical trials with MitraClip (Abbott Laboratories, Abbott Park, Illinois, USA): the MITRA-FR presented at the congress organized by the European Society of Cardiology and the COAPT presented at the Transcatheter Cardiovascular Therapeutics (TCT) congress. Both trials have been discussed extensively. Could you please tell us what the basic differences are in the results obtained by these two trials?
ANSWER: The clinical studies MITRA-FR1 and COAPT2 share the honor of being the very first two studies in history with a rigorous design that randomized patients with functional mitral regurgitation (FMR) to receive optimal medical therapy or optimal medical therapy plus the FMR correction device MitraClip. There were opposing results. In the MITRA-FR the device did not produce any benefits over the composite event of death or rehospitalizations after one year of follow-up. In the COAPT, the Mitra- Clip group showed a significant reduction of hospitalizations at 2 years, and a reduced composite endpoint of death/rehospitalizations at 2 years. It seems reasonable to try to analyze the differences between both studies in an attempto to understand these opposing findings. These are the most significant differences I have seen:
- Magnitude of the FMR. This is probably one of the most important aspects that may explain the differences seen. According to the clinical guidelines established by the ESC, the MITRA-FR included patients with severe FMR defined as an effective regurgitant orifice area (EROA) ≥ 20 mm2 or regurgitation volumes > 30 mL. This brought these patients’ average EROA to 31 ± 10 mm2. On the contrary, according to the American clinical guidelines,3 the COAPT considered significant FMR EROAs ≥ 30 mm2 or regurgitation volumes > 45 mL (average EROA 41 ± 15 mm2). Also, in the MITRA-FR over half of the patients (52%) showed EROAs between 20 and 30 and in the COAPT, 87% of the patients showed EROA values > 30 mm2. In sum, the COAPT included patients with more severe FMR which would, logically, have a bigger impact on the patients’ events when corrected.
- Ventricular volumes. The patients from the MITRA-FR showed higher average ventricular volumes compared to those from patients from the COAPT (end-diastolic volume index: 135 ± 35 mL/m2 versus 101 ± 34 mL/m2). This means that the disease was far more advanced in the French study compared to the American study. This can also be one of the keys that may explain the differences seen. Treating some FMR in patients with very dilated ventricular volumes may have no effect at all on major cardiovascular events.
- Optimal medical therapy. This is another essential aspect if we want to understand the differences seen between both trials. In the MITRA-FR, the medical treatment that patients were receiving before randomization was the one the treating physician considered optimal. Also, this treatment could be modified during follow-up without the study committee knowing about it. Thus, even though the drug doses administered to manage heart failure may have been the correct ones at the beginning of the study, they may have been modified later on. And it is well-known that optimizing drug doses has a major impact on patients’ events and functional class. This effect can be seen in the functional class improvement experienced by the group that received medical treatment in the MITRA-FR. However, in the COAPT an «eligibility committee» monitored that every patient would receive the right drugs and the maximum tolerated doses before randomization. That’s why there were not too many dose modifications in the COAPT follow-up compared to the beginning of the trial.
- MitraClip performance. There are substantial differences when it comes to the level of success and performance achieved by this device. In the MITRA-FR, 9% of the patients never received the device. The number of complications was higher in the MITRA-FR (14.5% versus 8.5%) and the percentage of success at one year was lower in the French trial (17 versus 5% with FMR > 2+).
- Selection of candidates. The COAPT trial paid special attention to the selection of candidates. Patients whose baseline characteristics offered poor prognosis in the short-term and in whom the intervention wouldn’t probably lead to significant clinical improvements were excluded. Irreversible pulmonary hypertension, moderate or severe right ventricular dysfunction, stage D heart failure, hemodynamic instability, and inotropic therapy were cause for exclusion from the trial. These patients were not in the exclusion list presented by the MITRA-FR. Also, all patients from the MITRA-FR should have been hospitalized, at least, one time before joining the trial, but the COAPT never considered this as a prerequisite which favors the selection of a less evolved population. The possible inclusion of these cases added to the inclusion of patients with ventricles in a far more advanced stage of the disease and not too much mitral regurgitation may have been decisive and explain the results obtained.
- Follow-up time. In the COAPT, survival curves start to separate clearly after one year of follow-up. The MITRA-FR has one year of follow-up only. We may see a different progression of these patients in time, in this study, as follow-up goes on.
- Methodological aspects. The minimum primary endpoint of the MITRA-FR was a composite of rehospitalizations or death at one year. In order to analyze this variable, the Kaplan-Meier survival analysis was used which, even though is correct from the methodological point of view, it presents us with one problem: rehospitalization is an event that may occur in time but this analysis does not take it into consideration. This is especially important here since one of the problems of this type of patients is the number of rehospitalizations. Being hospitalized once or five times a year is certainly not the same. This is something that the MITRA-FR did not pay attention to. On the other hand, the COAPT was actually designed to analyzed recurring events. As a matter of fact, the COAPT primary endpoint was the number of rehospitalizations at 2 years (not only if the patient was admitted or not). The COAPT included a composite of death/rehospitalizations as a secondary endpoint, but the way it analyzed this varies from the MITRA-FR. The events death and hospitalization are not exclusionary, but one is more relevant than the other. In the MITRA-FR, both events were considered the same and the only thing that would cancel the survival analysis was suffering from one or the other, whichever would come first. However, the COAPT had a more appropriate way to analyze this type of intercurrent events: the WIN ratio (the win/loss ratio in the treatment group). The WIN ratio analyzes the most important clinical event (death) giving it relevance even though it may have occurred after hospitalization. This way of analyzing the composite event shows differences that the traditional Kaplan-Meier model does not detect or does not detect so sharply.
Finally, we have to say that the COAPT was a more rigorous study than the MITRA-FR. In the French study, 43 patients were excluded from the protocol in the MitraClip group due to several reasons which amounts to 28% of the sample in the intervention group. Also, the numerous losses of secondary variables such as quality of life, analytical values, functional class and, most surprisingly, control echocardiograms, leaves these events un-scrutinized in the study since they may be prone to bias. In this sense, the percentage of significant FMR relapses at one year is an approximate estimate and, therefore, inaccurate.
Q.: The virtues of the COAPT trial have been praised and the limitations from the MITRA-FR brought to everyone’s attention but, in your opinion, which would be the most positive aspects of the MITRA-FR and the most negative aspects of the COAPT?
A.: The positive aspects of the MITRA-FR are that it is the very first study to conduct a rigorous analysis on this issue by teaching us that choosing the optimal therapy for the management of heart failure and optimizing the maximum doses significantly improves patients and reduces their FMR (let’s not forget that we’re dealing with a dynamic process that can change in time). Also, maybe its most positive aspect is that it tells us what patients shouldn’t probably be eligible for this therapy: patients in advanced stages with not too much mitral regurgitation and without an optimized medical treatment. This subgroup of patients may have to be overlooked.
The negative aspects of the COAPT are that it was a lab experiment: all the variables were perfectly controlled, all treatments to their maximum doses, and the MitraClip device with an almost absolute success at 2 years. It will probably be difficult to replicate all this in the real world, but there is no doubt that it is the perfect example that FMR kills and that correcting it may lead to a substantial reduction of cardiovascular events. The COAPT trial sets the ideal we should aspire to in real life.
Q.: How do both studies complement each other to define what the ideal candidate for this technique really looks like?
A.: The interesting thing about these studies is that they should be implemented together to set the foundations of how we should choose the candidates. It seems obvious that we have to forget about patients in advanced stages (greater ventricular dilation), non-severe FMR and without optimal treatments. If we want to have more positive results, our candidates need to be in the early stages of the disease, have a significant degree of FMR (that really contributes to the clinical situation), be perfectly treated, and have good results with the device (which means that the anatomical selection and the experience of the interventional team need to be high). However, we always have to be cautious with assumptions like these. These data show the «average» patient, but a COAPT trial subanalysis reveals that as long as the FMR is very relevant (EROA > 30 mm2) there will always be a benefit, regardless of the degree of ventricular dilatation. That’s why every case should be treated individually, and in my opinion, we should be very serious about the amount of FMR. On top of reducing major events, MitraClip also improves quality of life and functional class. These are goals that we should take into account when selecting patients because this may be the only therapy that will alleviate very advanced symptoms.
Q.: In the last TCT we also saw the results from a smaller clinical trial, the REDUCE-FMR, that evaluated a system of percutaneous annuloplasty. Given the results of MitraClip, which could be the role of percutaneous annuloplasty systems in patients with heart failure and severe FMR?
A.: In the COAPT study, the results from the clip were excellent because the anatomical selection of the candidates was excellent as well. However, in the real world we won’t find cases like this all the time. In my opinion, in patients with great annular dilatation, so big that will prevent leaflet coaptation, the clip may have suboptimal results. It is in these cases where the role played by percutaneous annuloplasty systems may be essential - alone or in combination with the clip. According to the COAPT, the idea is that we should leave as little FMR as possible and that repair should be long-lasting, because this is what will eventually lead to less cardiovascular events. Percutaneous annuloplasty systems will complement our therapeutic arsenal to achieve this goal. However, to be taken into consideration, they need to show the same safety and efficacy profile as MitraClip.
Conflicts of interests
R. Estévez-Loureiro is proctor for MitraClip and declares to have received a research grant from Abbott Vascular.
Bibliografía
1. Obadia JF, Messika-Zeitoun D, Leurent G, et al.; for the MITRA-FR Investigators. Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med. 2018;379:2297-2306.
2. Stone GW, Lindenfeld J, Abraham WT, et al.; for the COAPT Investigators. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018;379:2307-2318.
3. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135:e1159-e1195.
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