Clinical Conference Proceedings: IAGS 2024 Summary Document

IAGS 2024 Writing Group: J. Dawn Abbott, MD; George Adams, MD; Nicholas Amoroso, MD; Herbert Aronow, MD; Itsik Ben-Dor, MD; Sam Conaway, MBA; Megan Coylewright, MD; Eric Dippel, MD; Dmitriy Feldman, MD; Kirk Garratt, MD; Adam Greenbaum, MD; George Hanzel, MD; Jimmy Kerrigan, MD; Ayman Magd, MD; Sundeep Mishra, MD; Piotr Musialek, MD; Jihad Mustapha, MD; Sigrid Nikol, MD; William O'Neill, MD; Rajan Patel, MD; Charanjit Rihal, MD; Michael Rinaldi, MD; Toby Rogers, MD, PhD; Souheil Saddekni, MD; Jonathan Schwartz, MD; Richard Smalling, MD, PhD; Molly Szerlip, MD; Jacqueline Tamis-Holland, MD; Alexander Truesdell, MD; Bonnie Weiner, MD; David Wood, MD. Faculty Disclosures

Program Director: Robert Bersin, MD

Compiled and edited by: Gary Rowbury, Laurie Onopa, H. V. (‘Skip’) Anderson, MD

Funding: These proceedings were funded by publication grants from Chiesi and W.L. Gore.

Session 1: Coronary Session 1 – Elective PCI

1.1       DCB’s for De Novo Coronary Lesions: Which Lesions and Are We There Yet? 

Problem Presenter:   J. Dawn Abbott, MD

Statement of the problem or issue

Drug-coated balloons (DCBs) combine an angioplasty balloon with an anti-proliferative drug. They have several potential advantages over metallic drug-eluting stents and bioresorbable scaffolds in maintaining coronary distensibility, vasomotor function, and preventing chronic inflammation which can lead to neoathrosclerosis. In the United States (US) there are no FDA-approved DCBs currently available, even though the first DCB was CE-marked in Europe in 2007, and they have been under investigation outside the US for more than a decade. There are currently 14 companies that manufacture paclitaxel-coated balloons, and several other DCBs using sirolimus or biolimus are under development. There has been a steady increase in DCB use outside of the US. In Japan, for example, they were first approved in 2014, and that year they were used in 6% of PCI procedures; last year it was 21% of interventions. So, over fifty thousand interventions were performed with DCBs.

Paclitaxel has many characteristics that make it well suited for DCB application. It is rapidly absorbed, taken up in the subintimal space, and then distributes to the adventitia. Drug persistence and durability in these tissues over long periods of time has been demonstrated. Its safety, although debated for a few years, has now been accepted, and the dosing is well worked out. Sirolimus, on the other hand, has presented a more difficult challenge because of certain biological and technical limitations. However, with new crystalline formulations, micro-reservoirs, and other new technologies, there are experimental data for sirolimus-coated balloons showing very effective drug concentrations in the vessel wall for up to 90 days. We will likely see several very effective DCBs available in the near future. Several of their purported advantages have been borne out. The most important one is that serial angiographic and OCT studies have shown that 40% to 50% of vessels treated with a DCBs will demonstrate positive remodeling on follow-up imaging, not to the degree of being aneurysmal, but allowing for vessel growth, which is not allowed with metal scaffolds.

Gaps in current knowledge

There is limited experience with non-paclitaxel anti-proliferative formulations. Furthermore, clinical data are limited for most lesion and patient subsets of interest, for example, in long lesions, bifurcations, and in patients with acute coronary syndromes (ACS). The largest amount of available data relates to in-stent restenosis and small vessels.

The optimal delivery method is not yet understood. Sometimes DCBs are bulkier devices than regular balloons, and the anti-proliferative drugs only reside on the balloon surface for a certain amount of time. Efficient catheter delivery to the target vessel is very important. In a retrospective study which examined DCBs delivered through a Guideliner versus regular direct delivery, there was a lower rate of TLR in the Guideliner-delivery group, despite the target lesions being a much more anatomically complex group. This raises important questions: If you can't get the DCB rapidly to the target lesion, how effective will it really be?

Another gap area is methodology and criteria to assess immediate procedural outcome. Outside the US, consensus groups have proposed residual stenosis <30%, presence of TIMI-III flow, FFR > 0.8, and absence of deep medial dissections or type C or greater dissections.

Device cost and reimbursement will be major issues, especially in the United States. Now that drug-eluting stents are typically under $300, how will DCBs compete with these low prices? If DCBs are reimbursed at balloon angioplasty rates, it will be difficult to achieve substantial uptake among interventionalists.

Possible solutions and future directions

Physician training is paramount. The DCB industry has taken on much of the responsibility for controlled release of new devices and insuring that physicians are trained to use their products. Post-marketing surveillance registries and other clinical registries will be key to understanding the adoption of DCBs and tracking outcomes. In the United States, as seen with other new devices, randomized trials examining patient and lesion subsets will help. Eventually, guidelines and consensus statements will be developed which will assist clinicians with: (1) selecting appropriate patients and lesion types for DCB treatment; (2) assessing techniques for optimal vessel and lesion preparation; (3) providing algorithms that outline when a DCB-only strategy is acceptable and scenarios in which a bail-out stent approach should be considered. Techniques for rapid and efficient device delivery will also have to be examined. Finally, artificial intelligence could potentially be used to review millions of procedures and look at characteristics that would be favorable for DCB intervention. For example, are intermediate lesions or vulnerable plaques appropriate candidates for DCB treatment?

Reference

1. Jeger RV, Eccleshall S, Wan Ahmad WA, et al. Drug-coated balloons for coronary artery disease: Third Report of the International DCB Consensus Group. JACC Cardiovasc Interv. 2020;13(12):1391-1402.

1.2       Plaque Modification: When to Apply Ablative vs Disruptive Therapies

Problem Presenter:   Jacqueline E. Tamis-Holland, MD

Statement of the problem or issue

Severe calcium is noted in target coronary lesions in about 18% to 26% of patients undergoing PCI.^1,2 Importantly, calcium is associated with greater procedural complication rates, lower procedural success rates, and higher rates of restenosis and stent thrombosis. Plaque modification techniques can improve initial PCI success rates in calcified coronary lesions, however, they are used in <10% of PCI procedures overall, and there is wide variability across hospitals.³ For example, rates of coronary atherectomy range from <2% up to 15% of PCI procedures. Some of this variability in use may be due to institutional factors (availability of devices) along with operator-comfort levels. Over the past decade there has been a steady increase in use of plaque modification techniques, most notably since the introduction of intravascular lithotripsy.⁴

The approach to the treatment of calcified lesions, and the decision to proceed with plaque modification is best determined with intracoronary imaging — either OCT or IVUS. Plaque modification is generally indicated when OCT images reveal the following features: An arc of calcium that is >180 degrees in extent, a calcified lesion length >5 mm, and calcification that is >0.5 mm in depth. With IVUS, a calcium arc of >180 degrees (but more specifically 270 to 360 degrees), and calcium >5 mm in length are indications for plaque modification. Angiographic criteria, such as dense calcium on both sides of the arterial wall, can also be used. Additionally, inability to deliver the IVUS catheter or other devices across the lesion is usually a reliable sign that plaque modification is needed.

Presently, there are 3 technologies available to assist in modifying heavily calcified coronary plaques. These include ablative and disruptive devices. Rotational atherectomy and orbital atherectomy are classified as ablative, while intravascular lithoplasty is classified as disruptive. The device configurations are illustrated in Figure 1. This figure does not include all devices. Some other devices include the laser catheter (which is technically classified as one of the ablative therapies), cutting or scoring balloons (classified as ablative), and ultra-high pressure balloons (classified as disruptive). While these other devices have been used to treat calcified lesions, they generally have not been effective in cases of severe calcification.

Figure 1. Currently available plaque modification technologies.

Gaps in current knowledge

Despite improved procedural success and better stent expansion, randomized trial data have not consistently reported improvements in longer-term clinical outcomes with plaque modification devices. While use of plaque modification has increased over time, the rate of use is still quite low. This may be due to several factors. First, interventional cardiologists with lower volumes may not be comfortable using the ablative equipment. This equipment requires special training and/or proctoring and there is a learning curve that must be assimilated. Second, both rotational and orbital atherectomy catheters require special guidewires that are often difficult to deliver across tortuous lesions. On the other hand, intravascular lithoplasty catheters can be used with any guidewire and do not require formal training or proctoring. Selected comparisons of the 3 technologies are shown in the table. The listed features depict the strengths and limitations of each device and illustrate some of our gaps in knowledge. Most importantly, we lack full understanding of the appropriate niche or range of application for each device.

Table. Selected comparison of ablative and disruptive therapies.

Possible solutions and future directions

What are the unanswered questions we have, and what does the future hold? Is there an ideal technique to perform plaque modification? Can we derive algorithms to match lesion characteristics and overall anatomy that would favor one device and avoid the use of multiple devices? A recent review addressed this question and proposed a useful algorithm.⁵

Can existing devices be modified for easier use and better deliverability? This could facilitate greater device use by interventionalists. Finally, how can we ensure that operators across the country become comfortable in using devices for plaque modification?

References

1. Hemetsberger R, Abdelghani M, Toelg R, et al. Impact of coronary calcification on clinical outcomes after implantation of newer-generation drug-eluting stents. J Am Heart Assoc. 2021;10(12):e019815. doi: 10.1161/JAHA.120.019815. PMID: 34056911.
2. Lee MS, Yang T, Lasala J, Cox D. Impact of coronary artery calcification in percutaneous coronary intervention with paclitaxel-eluting stents: Two-year clinical outcomes of paclitaxel-eluting stents in patients from the ARRIVE program. Catheter Cardiovasc Interv. 2016;88(6):891-897. doi: 10.1002/ccd.26395. PMID: 26756859.
3. Beohar N, Kaltenbach LA, Wojdyla D, et al. Trends in usage and clinical outcomes of coronary atherectomy: A report from the National Cardiovascular Data Registry CathPCI Registry. Circ Cardiovasc Interv. 2020;13(2):e008239. doi: 10.1161/CIRCINTERVENTIONS.119.008239. PMID: 31973557.
4. Butala, NM, Waldo SW, Secemsky EA, et al. Use of calcium modification during percutaneous coronary intervention after introduction of coronary intravascular lithotripsy. JSCAI. 2024;3:101254. doi.org/10.1016/j.jscai.2023.101254
5. Barbato E, Gallinoro E, Abdel-Wahab M, et al. Management strategies for heavily calcified coronary stenoses: an EAPCI clinical consensus statement in collaboration with the EURO4C-PCR group. Eur Heart J. 2023;44(41):4340-4356. doi: 10.1093/eurheartj/ehad342. PMID: 37208199.

1.3       The Forgotten Side Branch in Bifurcation Lesions

Problem Presenter:   Ayman Magd, MD

Statement of the problem or issue

Does every bifurcation lesion require 2 stents, or only just 1? That is, should operators routinely stent both the main branch (MB) and the side branch (SB), or the main branch only? And if judgement and selectivity with SB treatment are needed, then, in which cases, and how do we judge? If we do use 2 stents, are there major differences in stent-placement techniques? Perspectives on these questions have shifted back and forth over the years. For a long time, there was a myth that a near-perfect angiographic result in a bifurcation lesion ensured the best long-term outcome. But the reality is, angiographically, a bifurcation lesion is going to look much better with two stents, however, the long-term outcome is a totally different matter.

Gaps in current knowledge

Early data showed that restenosis was more frequent in the SB than the MB, until the DEFINITION trial was published, which showed the opposite. In that trial, the expectation was that 2 stents would be better, but then it turned out, for example, there was no difference in mortality. The main issues were target vessel MI and TLR: The differences in these 2 outcomes were dramatic beginning the first day.

The same finding was observed in the DK-CRUSH trial where provisional stenting for left main bifurcation lesions was compared to a routine 2-stent strategy using DK-crush technique. There was improvement in target lesion failure (TLF), but, importantly, the difference emerges from the first day onward (Figure 2).

Figure 1. Target lesion failure (TLF) in the DK-CRUSH trial. From: J Am Coll Cardiol. 2017;70(21):2605–2617.

The concordant findings on early outcomes in these 2 trials suggest there were problems, and very likely it's an operator-dependent issue. This is an enormous gap area, and it confounds objective evaluation and hinders reproducibility.

Possible solutions and future directions

There are many different types of side branches. Are they all relevant? Are they all equally important? Should we put a lot of effort into trying to determine if we need to treat both branches? There are 2 important considerations that may point the way to future directions. First, there is length of the lesion in the SB. A network meta-analysis showed that with longer lesions in the SB (≥10 mm) a 2-stent strategy may be better than a provisional strategy.

Figure 2. Influence of side branch lesion length on clinical outcomes. From: JACC Cardiovasc Interv. 2020;13(12):1432-1444.

The second consideration is the amount of myocardium supplied by the SB. This can be characterized as fractional myocardial mass, that is, the fraction of total myocardial mass supplied by the SB. Comparing SBs to MBs, the SBs very often perfuse much smaller amounts of myocardium, and therefore may not be “significant” in about 80% of cases. Avoidance of the SB may then simplify the procedure. Figure 3 illustrates the issue.

Figure 3. Fractional myocardial mass (FMM) of coronary artery bifurcations. From: JACC Cardiovasc Interv. 2017;10(6):571–581.

In the present era, it seems that provisional stenting of bifurcation lesions is indicated, reserving treatment of SBs to certain specific situations. A typical recommendation is shown in Table 1 below.

Table 1. When to treat the side branch (SB) after treating the main branch in coronary bifurcations.

Finally, we don’t know which 2-stent technique is better. Clinical trials comparing DK-crush operators to Culotte operators would be helpful to better understand the influence of operator experience and bias.

References

1. Zhang JJ, Ye F, Xu K, et al. Multicentre, randomized comparison of two-stent and provisional stenting techniques in patients with complex coronary bifurcation lesions: the DEFINITION II trial. Eur Heart J. 2020;41(27):2523-2536. doi: 10.1093/eurheartj/ehaa543 PMID: 32588060
2. Chen, S, Zhang, J, Han, Y. et al. Double kissing crush versus provisional stenting for left main distal bifurcation lesions: DKCRUSH-V randomized trial. J Am Coll Cardiol. 2017;70(21):2605–2617. Epub 2017 Oct 30. doi: 10.1016/j.jacc.2017.09.1066
3. Di Gioia G, Sonck J, Ferenc M, et al. Clinical outcomes following coronary bifurcation PCI techniques: A systematic review and network meta-analysis comprising 5,711 patients. JACC Cardiovasc Interv. 2020;13(12):1432-1444. doi: 10.1016/j.jcin.2020.03.054 PMID: 32553331
4. Kim, H, Doh, J, Lim, H. et al. Identification of coronary artery side branch supplying myocardial mass that may benefit from revascularization. JACC Cardiovasc Interv. 2017;10(6):571–581. doi: 10.1016/j.jcin.2016.11.033

Session 2: Structural Session 1 - Aortic Valve

2.1       TAVR for Aortic Insufficiency: Latest Devices and Do We Have “Sufficient” Evidence?

Problem Presenter:   Itsik Ben-Dor, MD

Statement of the problem or issue

Comprehensive screening studies have shown repeatedly that aortic valve regurgitation (AR) is common, and, in general, is found more frequently than aortic valve stenosis (AS). In the OxVALVE study, the HONU community study, and a large study from Guangzhou, China, AR was first or second in frequency for valvular defects, between 4% to 8% of screened patients, whereas AS was much less common, between 0.5% to 2%.^1,2,3 Interestingly, when echo and cardiac magnetic resonance imaging (cMRI) imaging are performed and compared for the same patients, cMRI identifies AR more frequently and in greater severity than echo imaging.^4,5 This finding has led to efforts to redefine the parameters used for classifying “severe AR,” which in turn will change guideline recommendations for invasive therapies. Already, the US and European guidelines have begun to differ somewhat on definitions and recommendations for AR. For example, in US guidelines, LV systolic dysfunction is defined as LVEF ≤55%, whereas in European guidelines it is defined as LVEF ≤50%.

Critically, long-term survival in patients with AR is not favorable. Over time, as LV dimensions enlarge due to chronic volume overload, and LV performance deteriorates, symptoms of heart failure develop. With severe symptoms (NYHA Class II-IV) mortality may be greater than 70% at 5 years. (Figure 1).⁶

Figure 1. Survival in patients with AR by NYHA class. From: EuroIntervention 2013;10;9 Suppl:S55-62.

Surgical aortic valve replacement (SAVR) improves long-term outcomes in AR compared to medical therapy. The survival benefits appear to be greater for patients with more impaired LV function (LVEF<50%) compared to patients with normal LV function (Figure 2). However, the problem is that many patients with severe symptomatic AR and low LVEF are deemed “too high risk” for surgery. The Euro Heart Survey reported that only 37% of patients with LVEF >50% underwent SAVR, only 22% with LVEF 30%-50%, and only 3% with LVEF <30%.⁷

Transcatheter aortic valve replacement (TAVR) has now begun to be performed for isolated AR, that is, even when there is no AS present. Many issues regarding TAVR for AR remain to be settled. New valves are under development or investigation.

Figure 2. Survival in patients with AR by treatment. (Red curves = SAVR.  Blue curves = Medical therapy). From: Structural Heart. 2021;5:608-618.

Gaps in current knowledge

There are several areas that need clarification in TAVR for AR. For one, technologies for anchoring the device require improvement. Current valves often have insufficient anchoring. With AR, the aortic root is often dilated and the annulus is enlarged. When this dilated and enlarged anatomy is coupled with insufficient anchoring, this can lead to valve dislocation and possible embolization. The question of valve durability over many years of implanted life requires further studies. Additionally, how to approach AR when left ventricular support devices (LVAD) are in place, or needed, will require creative investigations.

Possible solutions and future directions

Examples of newer aortic valve designs that may be applicable for TAVR in AR are shown in Figure 3.

Figure 3. Newer aortic valves for TAVR in AR.

• Myrval Octacor
• Trilogy
• J-valve
• Hanchor valve
• Laguna Tech (self-expanding valve)
• Laguna Tech (balloon expandable valve)

Studies underway or planned will help us answer many of the remaining questions. We do have sufficient evidence that untreated severe AR is associated with worse outcomes compared to surgical treatment (SAVR). Many new transcutaneous valve devices are becoming available. The field of TAVR for AR is only just in its infancy.

References

1. d'Arcy JL, Coffey S, Loudon MA, et al. Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study. Eur Heart J. 2016;37(47):3515-3522. Epub 2016 Jun 26. doi: 10.1093/eurheartj/ehw229 PMID: 27354049; PMCID: PMC5216199
2. Gössl, M, Stanberry, L, Benson, G. et al. Burden of undiagnosed valvular heart disease in the elderly in the community: Heart of New Ulm Valve Study. J Am Coll Cardiol Img. JACC Cardiovasc Imaging. 2023;16(8):1118-1120. Epub 2023 Apr 12. doi: 10.1016/j.jcmg.2023.02.009.
3. He S, Deng H, Jiang J, et al. The evolving epidemiology of elderly with degenerative valvular heart disease: The Guangzhou (China) Heart Study. Biomed Res Int. 2021;2021:9982569. doi: 10.1155/2021/9982569 PMID: 33981773; PMCID: PMC8088353.
4. Kammerlander AA, Wiesinger M, Duca F, et al. Diagnostic and prognostic utility of cardiac magnetic resonance imaging in aortic regurgitation. JACC Cardiovasc Imaging. 2019;12(8 Pt 1):1474-1483. Epub 2018 Nov 15. doi: 10.1016/j.jcmg.2018.08.036 PMID: 30448117.
5. Neisius U, Tsao CW, Hauser TH, et al. Aortic regurgitation assessment by cardiovascular magnetic resonance imaging and transthoracic echocardiography: intermodality disagreement impacting on prediction of post-surgical left ventricular remodeling. Int J Cardiovasc Imaging. 2020;36(1):91-100. Epub 2019 Aug 14. doi: 10.1007/s10554-019-01682-x. PMID: 31414256
6. Roy D, Sharma R, Brecker SJ. Native aortic valve regurgitation: transcatheter therapeutic options. EuroIntervention. 2013;10;9 Suppl:S55-62. doi: 10.4244/EIJV9SSA11 PMID: 24025959
7. Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. Eur Heart J. 2003;24:1231-1243. doi: 10.1016/s0195-668x(03)00201-x PMID: 12831818.
8. Thourani VH, Brennan JM, Edelman JJ, et al. Treatment patterns, disparities, and management strategies impact clinical outcomes in patients with symptomatic severe aortic regurgitation. Structural Heart 2021;5:608-618. doi: 10.1080/24748706.2021.1988779

2.2       Lifelong TAVR Management and How to Deal with Leaflet Degeneration

Problem Presenter:   George Hanzel, MD

Statement of the problem or issue

Last year there were over 100,000 TAVR procedures performed worldwide, and there are presently approximately one million patients living with TAVR valves. Procedures are now being performed in younger and lower-risk patients, and therefore lifelong management of these patients must be considered. Leaflet degeneration of implanted TAVR valves will necessitate increasing numbers of TAV-in-TAV procedures in the future. One of the most important considerations with TAV-in-TAV is prevention of coronary artery obstruction. Some of the mechanisms of coronary obstruction after TAV-in-TAV include: (1) Direct coronary obstruction; (2) Sequestered coronary sinus; (3) Skirt or strut interference; (4) Commissural misalignment. (See Figure 1). It is estimated that 10%-25% of TAVR patients might not be candidates for TAV-in-TAV due to high risk for coronary obstruction. Factors that influence risk for obstruction include: (1) Anatomic (coronary height, sinus of Valsalva diameter, sinotubular junction height and diameter); (2) index procedural factors (index valve design, implant depth, commissural alignment); (3) TAV-in-TAV factors (valve choice, possibility for expansion of index valve, depth of TAV-in-TAV implant). Valve design and leaflet modification techniques are the primary approaches to dealing with potential coronary obstruction. Novel valve designs may help obviate coronary obstruction, but implantation technique and valve positioning may still put the coronaries at risk.

Figure 1. Valve features and risk of coronary obstruction with TAV-in-TAV. From: JACC Cardiovasc Interv. 2022;15:1777–1793.

Gaps in current knowledge

Almost everything about TAV-in-TAV is a knowledge gap area.

1. What percentage of TAVR patients will not be candidates for TAV-in-TAV? Only several small studies have explored this.

2. What is the risk of TAVR explant for structural valve deterioration? Current studies include many patients with endocarditis as well as high surgical risk patients which may skew outcomes.

3. In which patients will balloon-assisted BASILICA be feasible to prevent coronary occlusion or sinus sequestration? Can dedicated devices improve procedural efficiency and success?

4. Is leaflet excision a pipe dream? With evolution of technology will leaflet excision become the dominant form of leaflet modification? What is the stroke risk? 

Possible solutions and future directions

Preventing or mitigating coronary obstruction is the most important objective. Some options for accomplishing this are outlined in Table 1.

Table 1. Options to mitigate risk of coronary obstruction in TAV-in-TAV.

• Assessment at the index procedure whether TAV-in-TAV is likely in the patient’s future. If not, then should SAVR be the first intervention, especially in young, low-risk patients?
• Careful implantation technique to increase likelihood of future TAV-in-TAV success (e.g. commissural alignment; lower rather than higher implant position)
• Don’t perform TAV-in-TAV
  • Consider medications (no intervention)
  • Consider TAVR explant and SAVR
• Snorkel stenting not an option (interaction with valve stent frame – crushing of stent between valve frames)
• BASILICA (bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction – Figure 2)
  • Traditional BASILICA yields minimal splay since leaflets are constrained by TAVR valve frame
  • Balloon-assisted (BA-)BASILICA provides greater splay and therefore increased coronary perfusion. (>20% more in bench-top models).
  • Dedicated leaflet laceration devices may streamline procedure
  • Commissural misalignment may preclude BA-BASILICA
• Leaflet excision
  • CATHEDRAL – transcatheter leaflet removal using electrified wire (Figure 3).
  • SURPLUS – surgical leaflet removal with concomitant TAVR.

Figure 2. Balloon-assisted BASILICA for leaflet modification. From: JACC Cardiovasc Interv. 2021;14(5):578–580 and Circ Cardiovasc Interv. 2021;14(11):e011028.

Figure 3. The CATHEDRAL procedure for leaflet excision. From: JACC Cardiovasc Interv. 2022;15(16):1678-1680

References

1. Tarantini, G, Sathananthan, J, Fabris, T. et al. Transcatheter aortic valve replacement in failed transcatheter bioprosthetic valves JACC Cardiovasc Interv. 2022;15(18):1777–1793. doi 10.1016/j.jcin.2022.07.035
2. Greenbaum, A, Kamioka, N, Vavalle, J. et al. Balloon-assisted BASILICA to facilitate redo TAVR. JACC Cardiovasc Interv. 2021;14(5):578–580. doi.10.1016/j.jcin.2020.10.056
3. Perdoncin E, Bruce CG, Babaliaros VC, et al. Balloon-augmented leaflet modification with bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction and laceration of the anterior mitral leaflet to prevent outflow obstruction: benchtop validation and first in-man experience. Circ Cardiovasc Interv. 2021;14(11):e011028. doi: 10.1161/CIRCINTERVENTIONS.121.011028 PMID: 34674556
4. Babaliaros VC, Gleason PT, Xie JX, et al. Toward transcatheter leaflet removal with the CATHEDRAL procedure: CATHeter Electrosurgical Debulking and RemovAL. JACC Cardiovasc Interv. 2022;15(16):1678-1680. doi: 10.1016/j.jcin.2022.05.038 PMID: 35981843

2.3       TAVR for Moderate AS: Not So Fast

Problem Presenter:   Megan Coylewright, MD

Statement of the problem or issue

Aortic valve stenosis (AS) has an unfavorable prognosis. Severe AS is associated with high mortality. Aortic valve replacement (AVR) can improve prognosis, but even with replacement, many patients are still faced with symptoms and early mortality from heart failure due in part to the adverse hemodynamic effects of chronically high afterload on the left ventricle. Figure 1 illustrates 4-year mortality rates with and without AVR for various degrees of AS severity.

Figure 1. Mortality rates for various degrees of AS severity with and without AVR. From: J Am Coll Cardiol. 2023;82(22):2101-2109

While increased afterload from a stenotic valve contributes to cardiac damage, AS also is associated with concomitant conditions like hypertension, coronary artery disease, renal disease, and increasingly in the elderly population, frailty. Assessment of cardiac damage in AS, and methods to quantify it and better understand the implications for clinical outcomes, are now underway. A growing body of data support the hypothesis that cardiac damage affects prognosis after AVR. Figure 2 illustrates a staging system for cardiac damage, and its effects on mortality and poor quality of life (QoL) measures after AVR.

Figure 2. Effect of cardiac damage from AS on mortality and QoL after AVR. From: J Am Coll Cardiol. 2023;81(8):743-752.

Gaps in current knowledge

It is clear that AS is both a valvular and a ventricular problem, and, therefore, AVR by either TAVR or SAVR often requires ongoing management of heart failure. This message is too often overlooked in patient education and shared decision making regarding an AVR procedure. The condition of the left ventricle prior to TAVR may be one of the key predictors of patient outcomes that could be modifiable.

An increasing focus on prevention and management may improve post-intervention health status and mortality. Earlier valvular intervention and use of guideline-directed medical therapy (GDMT) for both systolic and diastolic heart failure could be impactful. Specifically, the role of SGLT2 inhibition and use of ARNIs in moderate and severe AS are areas of focus currently.

Importantly, consideration of lifetime management of patients with AS is needed when considering earlier intervention. Patient goals and preferences may differ from that of the clinical team, and best practices for incorporating patient values into cardiovascular decision-making processes continues to be a focus of ongoing research.

Possible solutions and future directions

Ongoing randomized trials are evaluating the effect of earlier treatment of AS when moderate stenosis is identified, in conjunction with medical therapy, on quality of life and clinical outcomes like heart failure events and mortality. These trials are designed to answer the following questions:

• • How strong is the evidence that earlier AVR will improve ventricular function?
  • How are harms balanced with benefits when considering earlier AVR? (valve degeneration over time, pacemaker, coronary re-access)
  • How necessary is GDMT with SGTL2inh in moderate AS trials?
  • What are strengths and weaknesses of the “HF event” endpoint?
  • What will be the role for device-first strategies in structural heart interventions with heart failure as a primary endpoint?
  • How best to integrate patient goals and preferences in trial cycle and clinical decision making?

References

1. Généreux P, Sharma RP, Cubeddu RJ, et al. The mortality burden of untreated aortic stenosis. J Am Coll Cardiol. 2023;82(22):2101-2109. doi: 10.1016/j.jacc.2023.09.796 PMID: 37877909
2. Généreux P, Cohen DJ, Pibarot P, et al. Cardiac damage and quality of life after aortic valve replacement in the PARTNER trials. J Am Coll Cardiol. 2023;81(8):743-752. doi: 10.1016/j.jacc.2022.11.059 PMID: 36813373
3. Col NF, Otero D, Lindman BR, Horne A, Levack MM, Ngo L, Goodloe K, Strong S, Kaplan E, Beaudry M, Coylewright M. What matters most to patients with severe aortic stenosis? PLoS One. 2022;17(8):e0270209 PMID: 35951553

Session 3: Endovascular Session 1

3.1       DCBs, Stents and Endografts in Lower Extremity Interventions: What is Best? Leave Nothing Behind or a Lesion Specific Approach?

Problem Presenter:   Jihad Mustapha, MD

Statement of the problem or issue

We investigated the question of why success rates with lower extremity interventions decline as one moves down the arteries from the iliac to the superficial femoral (SFA), to the popliteal, and then below into the tibial arteries. We developed the hypothesis that there were histopathologic differences between these arteries, and these were, in part, responsible for the differences in success and failure.

Figure 1. Differences in morphology along the peripheral arteries of the extremity. From: JACC Cardiovasc Imaging. 2019;12:1501-1513.

The histopathology changes along the course of the arteries.¹ Above the knee there is intimal calcium, based on mechanisms that we're familiar with from the coronaries. Below the knee there are significant amounts of medial calcium. In between, there is a transitional zone. The medial microcalcification begins, at first very diffuse, but then it becomes punctate. Eventually, the media fragments. As you move into the tibial arteries, osteoblasts are present in the media, and osteophytes form, so there is active bone formation. There are two types of smooth muscle cells in the tibial arteries. One is a proliferative smooth muscle cell, and the other is a progenitor smooth muscle cell. So, when you see proliferation of smooth muscle cells into the lumen of the tibial artery, they're coming from the arterial wall. Formation of intimal calcium is much higher in the SFA, and it's much lower in the tibials. When you look at medial calcium, it's dominant in the tibial arteries. The proximal tibial may show some characteristics similar to the SFA, but it quickly transitions into more medial hyperplastic disease and medial calcification.

Gaps in current knowledge

Stents, even drug-eluting stents, have not been as successful below the knee as above the knee. The same is true for bioresorbable vascular scaffolds. The pathology of the arterial wall is different below the knee, with a dual smooth muscle cell system in the media, and when a stent is placed it excites an intense hyperplastic response with smooth muscle cell migration through the stent struts and into the lumen. Drug coated balloons (DCBs) have had better success below the knee since the antiproliferative drugs inhibit the hyperplasia and do not leave any residual mass behind like a stent does. While there are compelling data for the paclitaxel-coated balloons, data for the limus-family of drugs is not as extensive. Newer drug formulations and newer balloons are becoming available, and these will be tested in trials.

Possible solutions and future directions

At the present time the best approach is to leave nothing behind when possible.

References

1. Torii S, Mustapha JA, Narula J, et al. Histopathologic characterization of peripheral arteries in subjects with abundant risk factors: correlating imaging with pathology. JACC Cardiovasc Imaging. 2019;12(8 pt 1):1501-1513. doi: 10.1016/j.jcmg.2018.08.039. PMID: 30553660.

3.2       Endografts for Aortic Aneurysm: How do they ADVANCE? Stay in Bounds or Pay the Price? Suprarenal vs. Infrarenal Grafts? Or is Stabilization Therapy (EAST) the Answer?

Problem Presenter:   Sigrid Nikol, MD

Statement of the problem or issue

Nikolai Volodos implanted the very first stent graft in a stenotic iliac artery in 1985. Then, in 1987 he placed another stent graft into a traumatic aneurysm of the descending aorta. Independently from Volodos, Juan Parodi first implanted a stent graft of his own design into an aorta in 1990 in Argentina, and then again two years later in 1992 in the US. The first self-expanding stent grafts were implanted in 1993 by Michael Lawrence-Brown and David Hartley in Perth, Australia, and Krassi Ivancev in Malmo, Sweden. The first bifurcated stent graft was implanted the same year, 1993, by Tim Chuter in Aachen, Germany. The first fenestrated stent graft was implanted 1997, again by the Australians Lawrence-Brown and Hartley. The key points of stent graft development are summarized in Table 1.

Table 1. Key developments in aortic endografts.

The problem we realize now is we have a highly progressive underlying disease, which not only causes circumferential enlargement of the aorta, but also elongates or propagates up and down the aorta over time; in other words, we have disease progression.

Gaps in current knowledge

The basic problem is sealing. There must be a sufficient landing zone for an endograft, particularly for the proximal end, and there must be tight sealing here. The difficulties are: (1) angulated necks; (2) irregular necks which are calcified and thrombotic; (3) short necks. The patient may come back after 2 to 3 years with a Type 1 endo-leak because the landing zone may not have been adequate enough to achieve long-term sealing, and the patient may have had disease progression leading to further enlargement.

In addition to identifying appropriate landing zones, there is the problem of visceral branches. Manufacturers have developed fenestrated protheses as well as branched prostheses to deal with these. There is more experience with fenestrated prostheses than with the branched variety. However, the branched protheses are more forgiving if the pre-procedure measurements were slightly off, or if there is a twist during placement: it is possible to correct much better than with a fenestrated prosthesis. There are also prostheses containing both, that is, fenestrations in the upper section and branches in the lower section.

Possible solutions and future directions

Custom made prostheses rather than off-the-shelf designs are possible, but the prices are very high. Physician modified endografts are available, but these require meticulous planning, extensive experience, and highly technical training.

3.3       Carotid Artery Intervention: Comparative Outcomes of Micromesh Stents and TCAR and Are They Better Than CEA?

Problem Presenter:   Piotr Musialek, MD

Statement of the problem or issue

Stroke incidence and the number of stroke-affected patients will increase over the next 20 years. Medical therapies alone are not sufficient to reduce the risk of stroke in patients with carotid artery stenosis. The difficulty with medical therapies is: (1) the efficacy or “strength” of pharmacologic agents is low; (2) patient compliance is suboptimal. Carotid artery revascularization is and will be needed to reduce the risk of carotid-related stroke in many patients with carotid artery stenosis. Risk stratification tools are here today to help identify the patients who may need carotid revascularization – and they are improving.

The surgical approach to revascularization, carotid endarterectomy (CEA), removes the atherosclerotic plaque material. With carotid artery stenting (CAS), the concept is to stabilize the plaque. Ideally, we would like to totally isolate the plaque with CAS to achieve an effect similar to vascular surgery. The first generation of stents consisted of a single layer. Those stents had a “cheese grater” effect that allowed atherosclerotic debris to “squeeze through.” Today we have second generation dual layer carotid stents called micromesh stents, which have documented anti-embolic effects. (Figure 1).

Figure 1. Micromesh dual layer carotid artery stent. Photo courtesy of InspireMD.

Additionally, there is a hybrid strategy called transcarotid artery revascularization (TCAR). In this approach, there is surgical exposure of the common carotid artery for access, followed by catheter-based stent delivery. It is an evolving technique that is likely to lead to safer carotid artery revascularization in the future.

Gaps in current knowledge

Carotid artery stent trials have not been designed well. Historical trial data, dating from 15 to 20 years ago, are of no value today. An analysis of earlier trials and registries found that more comorbid patients, as well as symptomatic and medically high-risk patients, were treated with CAS rather than CEA, leading to large differences in outcomes that were unfavorable to CAS.^1,2 We do not have a randomized trial powered for clinical endpoints; not a single one. With adverse event rates at approximately 1%, an adequately powered trial would require thousands of patients. Furthermore, it would be enormously expensive.

Possible solutions and future directions

The CARMEN collaborators recently performed a large meta-analysis of contemporary trials and studies of CAS that employed second generation (micromesh) carotid stents, comparing clinical outcomes to a large cohort of patients undergoing CEA during the same time frame.³ There were approximately 103,000 CAS patients and 95,000 CEA patients included. Clinical outcomes are shown in Figure 2. The results were very favorable for CAS. The future is hopeful.

Figure 2. Forest plots of clinical outcomes of CAS and CEA in the CARMEN collaborators meta-analysis. From: J Cardiovasc Surg (Torino). 2023;64(6):570-582.

References

1. Gaba KA, Halliday A, Bulbulia R, Chana P. Procedural risks of carotid intervention in 19,000 patients. Ann Vasc Surg. 2021;70:326-331. doi: 10.1016/j.avsg.2020.06.030 PMID: 38385840
2. Columbo JA, Stone DH, Martinez-Camblor P, et al. Adoption and diffusion of transcarotid artery revascularization in contemporary practice. Circ Cardiovasc Interv. 2023;16(9):e012805. doi: 10.1161/CIRCINTERVENTIONS.122.012805 PMID: 37725675
3. Mazurek A, Malinowski K, Sirignano P, et al (CARMEN) Collaborators. Carotid artery revascularization using second generation stents versus surgery: a meta-analysis of clinical outcomes. J Cardiovasc Surg (Torino). 2023;64(6):570-582. doi: 10.23736/S0021-9509.24.12933-3 PMID: 32599106

Session 4: Coronary Session 2 - STEMI

4.1       COMPLETE Revascularization Following STEMI: Not Whether, When

Problem Presenter:   David Wood, MD

Statement of the problem or issue

Eight years ago, we did not perform multivessel intervention in ST-elevation myocardial infarction (STEMI), it was a Class III recommendation, that is, don't do it. We even had the CULPRIT-Shock trial, saying, just treat the culprit lesion. Now, after five or more additional trials, complete multivessel revascularization is a Class Ia recommendation. This is important, since 50% of patients with STEMI have multivessel disease present. But, we're not just leaving it at STEMI anymore. Now it's all the acute coronary syndromes (ACS) together; it’s STEMI and non-STEMI (NSTEMI), too. The only caveat with NSTEMI is you have to make sure you know which is the culprit lesion.

Gaps in current knowledge

The largest gap we have is the question of how to determine the approach, how to choose the strategy, for the treatment of the non-culprit lesion or lesions. Which ones should be treated and when should they be treated? Is it based on angiographic severity of stenosis? Is it based on the territory at risk? For intermediate lesions, is it based on FFR or iFR or IVUS? How are comorbidities like age and frailty factored into the decision? What if additional therapies will be required, like ablative treatment for a calcified lesion, how does that fit in? And if we decide to delay treatment for non-culprit lesions at the primary procedure, when should we come back and perform them? The next day? During the same hospital admission? After discharge at a later date? What are the criteria by which we should decide these questions?

Possible solutions and future directions

Clinical trials are underway that will provide additional insights into these issues.^1-6

References

1. IVUS Versus FFR for Non-infarct Related Artery Lesions in Patients With Multivessel Disease and Acute STEMI (FRAME-AMI2). NCT05812963.
2. Fractional Flow Reserve Guided Immediate Versus Staged Complete Myocardial Revascularization in Patients With ST-segment Elevation Myocardial Infarction With Multivessel Disease. NCT05967663.
3. Deferred Stenting in Patients With Anterior Wall STEMI. NCT03744000.
4. Predicting the Risk of Non-culprit Coronary Artery Disease After a Heart Attack (OCT-RISK). NCT05781087.
5. STaged Interventional Strategies for Acute ST-seGment Elevation Myocardial Infarction Patient With Multi-vessel Disease (STAGED). NCT04918030.
6. Post-Revascularization Optimization and PHysiological Evaluation of intermediaTe Lesions (PROPHET-FFR). NCT05056662.

4.2       Therapies to Minimize Myocardial Injury During STEMI

Problem Presenter:   William O’Neill, MD

Statement of the problem or issue

Many therapies have been investigated for reducing infarct size, and almost all have been failures in human clinical studies. One of the problems is that everything works in a pig model, but never works in humans. Nevertheless, the work of Bart Meyns and his colleagues in Belgium has demonstrated in an animal model that unloading the left ventricle during reperfusion is associated with a significant decrease in infarct size.¹ (Figure 1).

Figure 1. Infarct size in an animal model with and without LV unloading during reperfusion. From: J Am Coll Cardiol. 2003;41:1087-1095.

We used these concepts and data to perform a pilot trial in patients with anterior STEMI. Patients were randomly assigned to LV support with immediate reperfusion or LV support with reperfusion delayed for 30 minutes in order to unload the ventricle. Results stratified by myocardium at risk (sum of ST segment elevation) are shown in Figure 2.

Figure 2. Final infarct size by estimated area at risk, Door-To-Unload Pilot Trial. From: Circulation. 2019;139(3):337-346.

Gaps in current knowledge

We know there is a difference between LAD and non-LAD infarcts. With right coronary (RCA) or circumflex (LCX) occlusions, that is, non-anterior infarcts, the infarctions are all smaller, usually <10% of LV mass, and there is less time-dependence on reperfusion. On the other hand, with LAD (anterior) infarcts, which comprise about 40% of the treated STEMI population, there is definitely a time dependency on reperfusion. Reperfusion <2 hours after symptom onset results in smaller infarct size, between 2-to-3 hours infarct size doubles compared to <2 hours, and after about 3 hours there is little or nothing to be gained with reperfusion. So, it will be important to focus on early reperfusion for patients with larger anterior infarcts.

One of the gap areas we have, though, is the relationship between final infarct size and long-term clinical outcomes. There are studies that indicate long-term outcomes are improved in patients with smaller infarct sizes.³ (Figure 3).

Figure 3. Event-free survival at 2 years by final infarct size. From: JACC Cardiovasc Imaging. 2014;7(9):930-939

Possible solutions and future directions

Building upon the results of the D-T-U-Pilot trial, this concept of unloading the left ventricle for 30 minutes prior to reperfusion is being examined in the multicenter STEMI-DTU clinical trial.⁴ This trial should be completed before the end of 2024, and data should be forthcoming.

References

1. Meyns B, Stolinski J, Leunens V, Verbeken E, Flameng W. Left ventricular support by catheter-mounted axial flow pump reduces infarct size. J Am Coll Cardiol. 2003;41(7):1087-1095. doi: 10.1016/s0735-1097(03)00084-6
2. Kapur NK, Alkhouli MA, DeMartini TJ, et al. Unloading the left ventricle before reperfusion in patients with anterior ST-segment-elevation myocardial infarction. Circulation. 2019;139(3):337-346. doi: 10.1161/CIRCULATIONAHA.118.038269
3. van Kranenburg M, Magro M, Thiele H, et al. Prognostic value of microvascular obstruction and infarct size, as measured by CMR in STEMI patients. JACC Cardiovasc Imaging. 2014;7(9):930-939. doi: 10.1016/j.jcmg.2014.05.010
4. Primary unloading and delayed reperfusion in ST-elevation myocardial infarction: the STEMI-DTU Trial (DTU-STEMI). NCT03947619. ClinTrials.gov.

4.3       Therapies to Improve Microvascular Function During STEMI and PCI

Problem Presenter:   Jimmy Kerrigan, MD

Statement of the problem or issue

Infarct size in STEMI, and therefore clinical outcomes too, ultimately depend on the microvasculature of the myocardium, a subject that is actively being studied both in the acute setting and the chronic setting. There are several risk factors that can lead to potential microvascular dysfunction during and after primary PCI for STEMI. Microvascular dysfunction includes clogging of the microvasculature with platelet plugs, solid fibrin, and cellular debris. There may be embolization of thrombotic material or fragments of calcific plaque material, along with abnormal vasomotor function including vasospasm. A recent review illustrates some of the potential mechanisms causing microvascular obstruction (MVO).¹ (Figure)

Figure. Possible mechanisms of microvascular dysfunction in myocardial infarction. From: Nat Rev Cardiol. 2024. doi: 10.1038/s41569-023-00953-4. PMID: 38001231.

Gaps in current knowledge

Numerous investigations have led to increasing data suggesting that many possible therapies that once seemed very promising might instead be neutral, if not harmful. Some of these are listed in the table.

Table. Potential therapies to prevent microvascular dysfunction in myocardial infarction. PPCI = primary percutaneous coronary intervention; GP= glycoprotein; LV = left ventricular

Several potent antiplatelets agents and anticoagulants, for example, thrombolytics like alteplase and GP IIb/IIIa inhibitors, are now thought to be harmful when used routinely, with no benefit to the microvasculature, and they are now reserved for select settings such as large residual thrombus burden or persistent no-reflow. Potent P2Y12 antagonists were once thought to help improve outcomes, but pre-loading with large doses doesn't seem to matter. Recent analyses have found they can be given before, during, or after primary percutaneous coronary intervention (PPCI), and outcomes are the same. Vasoactive medications like adenosine or other vasodilators were studied in clinical trials and were found to be harmful in most patients. Aspiration thrombectomy is potentially harmful when performed routinely, and so it too is reserved for selected cases. Some early data on mechanical thrombectomy suggested this therapy was safe, but it does not appear that pivotal outcomes trials that might support routine use will be undertaken.  Clinical investigators examining intermittent coronary sinus occlusion (PICSO) presented pivotal trial findings at TCT-2023, and these data indicated no benefit in patients with STEMI.² Ongoing studies include the utility of percutaneous LVAD during PPCI, as well as studies of super-saturated oxygen (SSO₂).^3,4 Therefore, at present, there are no compelling data on how to prevent MVO from occurring in STEMI patients, or how to treat it.

Possible solutions and future directions

There is no doubt that potential therapies to prevent microvascular dysfunction in STEMI will continue to be created and tested. The door-to-unload (DTU) and AMIHOT trials appear to be the most promising underway at this time. Other novel potential pharmacotherapies that could help relieve MVO, targeting the harmful effects of endothelial damage, myocardial edema, and microvascular spasm, possibly used in conjunction with mechanical approaches, await development with the hope that this serious complication of STEMI can be ameliorated.

References

1. Galli M, Niccoli G, De Maria G, et al. Coronary microvascular obstruction and dysfunction in patients with acute myocardial infarction. Nat Rev Cardiol. 2024;21(5):283-298. doi: 10.1038/s41569-023-00953-4
2. De Maria GL. Pressure-controlled intermittent coronary sinus occlusion (PiCSO) in acute myocardial infarction: PICSO-AMI-I trial. Presented at: TCT 2023. October 25, 2023. San Francisco, CA.
3. https://clinicaltrials.gov/study/NCT03000270
4. https://clinicaltrials.gov/study/NCT04743245

Session 5: Structural Session 2 - Mitral and Triscuspid Repair

5.1       TMVR: Latest Transeptal Valves and Clinical Outcomes

Problem Presenter:   Molly Szerlip, MD

Statement of the problem or issue

Transcatheter mitral valve replacement (TMVR) has several important issues associated with it (Table 1). First of all, mitral regurgitation (MR) or mitral stenosis (MS) generally are found in extremely sick patients. They are most often elderly and have many comorbidities. As a clinical entity, MR is very heterogeneous; it's not just one disease, and that presents an enormous challenge. There is degenerative MR and functional MR. The degenerative-MR patients are those where the leaflets themselves have problems. In the functional-MR patients, it is not the valve itself that is the issue, it is everything around the valve, like the annulus, or a problem with the ventricle. Do we need the same devices for these? Is there one device that will fix all of these deficiencies? Finally, with these devices, there is need for anticoagulation. And often these are the highest risk patients for bleeding.

Table 1. Problem Areas Associated With TMVR.

Gaps in current knowledge

Just like everything else, the more we know, the more we don't know. For example, functional MR has multiple etiologies, and we don't know if you should treat them all the same way. Should we eliminate MR or just reduce MR? After all, M-TEER is already commercially available. And likewise, for MS, why does MAC develop in general anyway? And why is it always the little old woman that you can't fit a device in that has the worst MAC? Are we just throwing devices at disease processes that we don't truly understand? Technology is advancing so much faster than our knowledge of the underlying disease processes. Furthermore, with TMVR, what do we know about valve leaflet durability? This potentially is a big problem.

Figure. Examples of current transcatheter mitral valves.

Possible solutions and future directions

The directions we might follow in the future:

• • Repair versus replace, may follow the current surgical trends;
  • Developing a bail-out option where repair fails – still avoid surgery;
  • Leaflet splitting technologies and procedures;
  • Intravascular lithoplasty for highly-calcified tissues;
  • Technologies that minimize need for anticoagulation;
  • AI-based algorithms to help choose the right device for the right valve problem

References

1. Hensey M, Brown RA, Lal S, et al. Transcatheter mitral valve replacement: An update on current techniques, technologies, and future directions. JACC Cardiovasc Interv. 2021;14(5):489-500. Epub 2021 Mar 1. doi: 10.1016/j.jcin.2020.12.038

5.2       TEER vs. Tricuspid Valve Replacement: Where To Go Following TRILUMINATE

Problem Presenter:   Jonathan Schwartz, MD

Statement of the problem or issue

At the time of this presentation, there were no FDA-approved tricuspid devices in the USA. However, shortly after this presentation was made, both the Edwards EVOQUE transcatheter tricuspid valve and the Abbott TriClip received FDA approval for use in the USA. There are a few with CE mark in Europe, including the TriClip (2020), the PASCAL clip (2022), and the EVOQUE transcatheter valve replacement (2023). (Figure)

Figure. Tricuspid Clips and Transcatheter Tricuspid Valve.

In addition to these devices, there are also the CardioBand, Intrepid valve, TricValve, and Sapien valve family, but they are all infrequently used or remain in early stage trials.

Gaps in current knowledge

The largest gaps in knowledge are:

1. Which device for which patient at what moment?
2. Can left-sided valve procedures (TAVR, M-TEER, etc.) be combined with a tricuspid valve procedure?
3. What are the appropriate endpoints for clinical trials?
4. Do we need more devices, or more clinical trials of existing devices?
5. How should advanced imaging techniques, including 3D-ICE, cCTA, and cMRI be integrated into valve therapies?

Possible solutions and future directions

Many more devices are under development currently, ranging from benchtop models to early clinical feasibility studies. Subgroup analyses of existing and future trials will help refine the questions and point out new directions. Multimodality imaging protocols will be explored and perfected. Relevant clinical endpoints will be determined. Antiplatelet and anticoagulant regimens will be defined. Surveillance protocols and imaging modalities for both pre- and post-procedure will be established. The future is wide open and much remains to be done.

References

1. Sorajja P, Whisenant B, Hamid N, et al. Transcatheter repair for patients with tricuspid regurgitation. N Engl J Med. 2023;388(20):1833-1842. doi: 10.1056/NEJMoa2300525
2. Kodali S, Hahn RT, Makkar R, et al. Transfemoral tricuspid valve replacement and one-year outcomes: the TRISCEND study. Eur Heart J. 2023;44(46):4862-4873. doi: 10.1093/eurheartj/ehad667

5.3       Novel Devices for Interventional Tricuspid Repair: A Better “Mouse Trap”?

Problem Presenter:   Charanjit (Chet) Rihal, MD

Statement of the problem or issue

The range of tricuspid valve pathology is huge, and it's even more heterogeneous than mitral valve pathology. Figure 1.

Figure 1. Examples of Tricuspid Valve Pathology (courtesy of Joseph Maleszewski, MD).

Annular dilatation of the tricuspid valve is the rule, and this leads to substantial tricuspid regurgitation, which then leads to volume overload of the right ventricle, and this results in massive dilatation of the right heart. Figure 2.

Figure 2. Annular dilatation of the tricuspid valve. Dilatation of the right heart (courtesy of Joseph Maleszewski, MD).

Gaps in current knowledge

1. Current procedures to repair or replace the tricuspid valve have many challenges. They are often long and tedious, with numerous technical challenges including imaging and the assessment of results. New technologies are being developed which will help address many of these challenges, but at present they remain in the early stages of design and development, and very early-stage clinical research.
2. An important issue is the appropriate time to intervene. Historically, there has been little we can offer patients with tricuspid regurgitation other than diuretics or high-risk surgery. Intervening too early would potentially expose a patient to many more years with prosthetic materials in the heart. On the other hand, intervening too late may result in missing the “therapeutic window.” Tricuspid valve disease is in many ways a systemic disease, and new clinical severity scores such as TRIO have been developed for better risk prognostication.
3. Assessing and grading the severity of tricuspid regurgitation remains extremely challenging and attempts to standardize this are underway.

Possible solutions and future directions

The focus of this presentation is on 3 new technologies that hold the promise of safety and efficacy, along with shortened procedure times. None of these are FDA approved, and all 3 are in the early stages of testing in humans. Final judgment on applicability must await the results of early feasibility studies. Many other tricuspid technologies, for example, annuloplasty, are also being developed, but are beyond the scope of this presentation.

One technology that is fairly far along in development comes from a company called V-Dyne, based in Minneapolis-St. Paul, Minnesota. It has a unique design, and anchors onto the tricuspid annulus using a side-biting mechanism. It is delivered via the right femoral vein access and IVC. The valve is removable, repositionable, mobile, and can be aligned precisely to the tricuspid annulus. It does not depend on tricuspid leaflets for anchoring, and in selected cases pacemaker leads can be accommodated. It is currently being evaluated in an early feasibility study (Figure 3).

Figure 3. The V-Dyne Tricuspid Valve.

A second novel transcutaneous tricuspid valve replacement system is from Laplace Interventional, also based in Minneapolis-St. Paul Minnesota. This is a unique valve that is delivered via the right internal jugular vein. This valve is anchored into the RVOT and posterior tricuspid annulus; it does not require leaflet anchoring. Most of the procedure is performed using fluoroscopy. This technology has just begun early feasibility studies in the United States (Figure 4).

Figure 4. The Laplace Tricuspid Valve.

A final new technology to mention is the 2 cross-caval systems from Innoventric. These are true cross-caval systems in that there are no materials positioned in the tricuspid valve or annulus itself. Here, the function of the tricuspid valve is replaced by a tubular valve-equivalent structure placed in the superior and inferior vena cava, Figure 5. The Trillium system has small flaps on the struts that open and close and act as multiple small valves. The Unica system has 2 actual valves, one in the superior vena cava and one in the inferior vena cava. These 2 valves permit blood to flow from both cava into the right side of the heart but not backwards. These bicaval systems may be useful in a broad range of patients, particularly those with a very large tricuspid annulus. A potential downside is continued dilatation of the right atrium, since regurgitation of the valve itself is not affected. On the other hand, the body would remain protected from the effects of severe tricuspid regurgitation, and so patients are likely to benefit from this. This technology has been tested in humans overseas and is about to enter the United States in an early feasibility study.

Figure 5. The Innoventric Heterotopic Cross-Caval Portfolio.

So, these illustrate some of the exciting new possible technologies that are coming into the tricuspid valve space.

Conclusions. Innovation and investment are continuing rapidly in the tricuspid regurgitation space. No single technology has yet proven itself applicable to the entire spectrum of patients with tricuspid regurgitation, and it is likely that multiple technologies will be required in the future given the heterogeneity of tricuspid regurgitation pathology. The next few years will see an acceleration of research and development in this area.

Reference

Welle G, Hahn R, Lindenfeld J, et al. New approaches to assessment and management of tricuspid regurgitation before intervention. JACC Cardiovasc Interv. 2024,17(7):837–858. doi.org/10.1016/j.jcin.2024.02.034

Session 6: Structural Session 3 - Atrial and Ventricular

6.1       LAA Occlusion: Is the “Square Peg in a Round Hole” Problem Now Solved?

Problem Presenter:   Nicholas Amoroso, MD

Statement of the problem or issue

Left atrial appendage occlusion (LAAO) provides effective thromboembolic risk reduction with less bleeding in patients with atrial fibrillation and is non-inferior to oral anticoagulants. There is ongoing data collection in more contemporary trials, but previous trials have proven this premise. Clinical experience is largely based on 2 current devices, the Watchman and the Amulet.

The questions or issues at hand are shown in Table 1.

Table 1. Current Issues with LAAO. DRT = device-related thrombus; LAA = left atrial appendage; OAC = oral anticoagulants.

Gaps in current knowledge

I have grouped these gap areas into three major categories: (1) incomplete occlusion; (2) antithrombotics and device-related thrombosis (DRT); and (3) efficacy and best practices, as shown in Table 2.

Table 2. Gaps in Knowledge for LAAO. DRT = device-related thrombosis; LAA = left atrial appendage; OAC = oral anticoagulants.

Possible solutions and future directions

I have listed my ideas in Table 3. The quality of the devices and the procedures themselves are being called into question. An ideal LAA occlusion device should safely eliminate any flow into or out of the LAA and not implant any thrombogenic foreign material. This is not consistently achieved with current generation technology. Furthermore, we don’t have very good long-term follow-up data on patients with and without optimal implants, especially those without. Lacking these data, providers struggle with guiding optimal thrombotic risk reduction.

Given that the LAAO advantage is largely due to reduced bleeding risk compared to OAC, additional methods for decreasing or eliminating the need for any post-procedure antithrombotics are wanting. Without complete elimination of post-procedure antithrombotics, LAAO therapy does not provide superior options for patients with both prohibitive bleeding risk and simultaneously elevated atrial fibrillation-related thromboembolic risk. Evidence-based best practices are lacking at present, but if they could be developed they could improve the therapeutic and safety profiles and expand access. There is a need for LAAO across many demographic groups. However, availability of the therapy is not equitable, nor will it be without the concerted efforts of stakeholders.

Table 3. Future directions for LAAO. LAAO = left atrial appendage occlusion.

References

1. Blackshear JL and Odell JA, Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg. 1996;61(2):755-759. DOI: 10.1016/0003-4975(95)00887-X PMID: 8572814
2. Holmes DR Jr, Schwartz RS, Latus GG, et al. A History of Left Atrial Appendage Occlusion. Interv Cardiol Clin. 2018;7(2):143-150. PMID: 29526283 DOI: 10.1016/j.iccl.2017.12.005
3. Aberg H. Atrial fibrillation: I. A study of atrial thrombosis and systemic embolism in a necropsy material. Acta Med Scand. 1969;185(5):373-379. PMID: 5808636
4. Reddy VY, Sievert H, Halperin J, et al. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. Jama. 2014;312(19):1988-1998. doi: 10.1001/jama.2014.15192
5. Turagam MK, Reddy VY, and Dukkipati SR, EWOLUTION of Watchman left atrial appendage closure to patients with contraindication to oral anticoagulation. Circ Arrhythm Electrophysiol, 2019;12(4):e007257. doi: 10.1161/CIRCEP.119.007257
6. Alkhouli M, Ellis C, Daniels M. et al. Left atrial appendage occlusion: current advances and remaining challenges. JACC Advance. 2022, Dec, vol 1, no. 5.
7. Saw J, et al. SCAI/HRS expert consensus statement on transcatheter left atrial appendage closure. Heart Rhythm. 2023;20(5), May.
8. Sommer R, Kim J, Szerlip M, et al. Conformal left atrial appendage seal device for left atrial appendage closure: first clinical use. JACC Cardiac Interv. 2021;14(21):2368–2374.
9. Kar S. https://www.vumedi.com/video/a-revolutionary-approach-to-left-atrial-appendage-closure-laminar-early-clinical-experience/

6.2       Interventional Ventricular Remodeling in Heart Failure

Problem Presenter:   Toby Rogers, MD

Statement of the problem or issue

For heart failure patients who are ill enough to require a left ventricular assist device (LVAD) or heart transplant, is there anything we can do for them? For specific structural defects, like aortic stenosis, aortic insufficiency, mitral regurgitation, and tricuspid regurgitation, we can attempt to treat or correct the defect if that is involved. We can close certain intracardiac shunts such as septal defects if that is the cause, or in some cases we can create holes in their heart if we think it might help. We can resynchronize their ventricles, and, of course, we can give them medications. But this is not what I'm talking about today.

Gaps in current knowledge

The knowledge gap issue we have to address in this session is this: Can we remodel a failing ventricle with a transcatheter implant? Is there a device we can insert that can change the geometry of the ventricle and thereby make patients feel better? As I see it, there are three simple ways of doing this: (1) We can put a device on the endocardial surface (Figure 1A). Typically, in order to do that, a number of anchors must be placed. Unfortunately, some anchors might pull out, thereby reducing effectiveness of the device. (2) Another way of changing the geometry of a dilated ventricle is to put a device on the outside of the heart and cinch it down (Figure 1B). One of the challenges with this approach are important structures located on the outside of the heart, notably the coronary arteries (Figure 1, A-C, small red circles), which might be compressed and possibly occluded as the device is cinched. (3) One final way, perhaps a little provocative, is to place a device within the myocardium (Figure 1C). This potentially gets away from concerns about anchors pulling out or externally compressing coronaries.

Figure. 1. Concepts for changing ventricular geometry.

Possible solutions and future directions

One example of an endocardial approach is the Accucinch device, which is under clinical investigation now (Figure 2). This device lies on the left ventricular (LV) endocardial surface with a series of implanted anchors that are then connected with a tether. Once all anchors have been deployed, the tether is cinched down to pull the anchors together.

Figure 2. Endocardial implant (Accucinch).

An example of an epicardial approach is the Cerclage device (Figure 3). It sits partially within the coronary sinus, so it is truly epicardial, and partially within the right heart, so it completely surrounds the left ventricle. Since the coronary sinus lies over the top of the circumflex coronary artery in most patients, the device includes a coronary protection element so that when it is cinched down, it doesn’t compress the underlying coronary.

Figure 3. Epicardial implant (Cerclage).

Finally, this is an example of a new intramyocardial implant concept we will be testing in humans very soon (Figure 4). We call this Mirth, and the entire device lies within the LV myocardium. This device can be placed anywhere from base to apex, does not rely on anchors for fixation, and cannot compress any of the coronaries since it lies beneath them.

Figure 4. Intramyocardial implant (Mirth).

In conclusion, I have here outlined 3 interventional approaches to changing the geometry of a dilated and dysfunctional left ventricle. All 3 approaches are undergoing investigation for safety and efficacy.

6.3       Interventional Electrocautery: Open SESAME

Problem Presenter:   Adam Greenbaum, MD

Statement of the problem or issue

The opposite end of the spectrum from dilated cardiomyopathy, which is typically accompanied by thinning of the left ventricular (LV) walls, is hypertrophic cardiomyopathy, where the left ventricular wall is too thick and often misshapen. With hypertrophy, we want to reduce this thickness with ventricular septal reduction therapies. The overall goal is to enlarge the LV outflow tract (LVOT): (1) because there is obstruction to flow from a distorted septum (HOCM), causing symptoms; or (2) we want to create additional space needed to safely implant a transcatheter mitral valve. The treatment approach can be focal, for example using surgical myomectomy, or it can be nonsurgical and zonal, using alcohol septal ablation or radiofrequency (RF) ablation.

Gaps in current knowledge

Surgical myomectomy can be very effective in relieving symptoms from LVOT obstruction, but experience is critical, and so this approach is not widely applicable generally as outcomes are not as good at low volume centers, in the elderly, and in patients with significant comorbidities. The advantage of a non-surgical, zonal approach is that it is less invasive. There are several disadvantages — they can be incomplete and leave residual obstruction, or there may be heart block with a need for a pacemaker. Also, later, scarring and fibrosis may produce late arrhythmias.^1,2

Possible solutions and future directions

A new percutaneous procedure has been developed, SEptal Scoring Along the Midline Endocardium (SESAME). It is an electrosurgical procedure that mimicks surgical myotomy, and first entails maneuvering a wire along a trajectory through the midline endocardium of the septum at a prespecified depth and length (Figure 1). Applying an electric current to the wire creates a myocardial laceration that splays apart over the subsequent days and weeks, ultimately enlarging the area to what is achieved with surgical myomectomy. This procedure has been used in over 100 patients in the US, with results from the first 76 patients treated at Emory University in Atlanta now published.³ In these selected patients, SESAME successfully reduced the median LVOT gradient at rest from 54 to 29 mmHg (p=0.023), and the median LVOT gradient under provocation from 149 to 85 mmHg (p=0.076). Assessment using computed tomography showed that septal thickness was reduced by one-half (16.4 mm to 8.5 mm) with most patients reporting improvement in symptoms. Clearly, clinical trials are needed to compare this promising new percutaneous procedure to other forms of therapy.

Figure. The SESAME percutaneous myotomy procedure. Image courtesy of Adam Greenbaum.

References

1. Elhadi M, Guerrero ME, Collins JD, Rihal CS, Eleid MF. Safety and outcomes of alcohol septal ablation prior to transcatheter mitral valve replacement. J Soc Cardiovasc Angio & Interv. 2022; doi: 10.1016/j.jscai.2022.100396.
2. Hoskins MH, Lisko JC, Greenbaum AB, et al. Septal bipolar ablation to prevent left ventricular outflow tract obstruction after transcatheter mitral valve implantation. Circ Cardiovasc Interv. 2023;16:e013333. doi: 10.1161/CIRCINTERVENTIONS.123.013333. PMID: 37712286.
3. Greenbaum AB, Ueyama HA, Gleason PT, et al. Transcatheter myotomy to reduce left ventricular outflow obstruction. J Am Coll Cardiol. 2024;83(14):1257-1272. doi: 10.1016/j.jacc.2024.02.007.

Session 7: Hemodynamics Session 1

7.1       Circulatory Support for Complex, High Risk PCI: How to Predict Who Benefits

Problem Presenter:   Sundeep Mishra, MD

Statement of the problem or issue

There are three very important issues in this field. First is oxygen supply to the myocardium, which is determined by myocardial perfusion pressure, or coronary diastolic pressure minus LV end-diastolic pressure (LVEDP). Second is oxygen demand of the myocardium, which is defined by pressure-volume (PV) loop area. Third is whole body circulation, which is determined by cardiac power product (CPO), or cardiac output multiplied by mean arterial blood pressure (MBP), then divided by 451 (See Figure 1). Normally, CPO is >1. Normal coronary perfusion pressure is typically between 60-to-80 (or, approximately 72 as shown in Figure 1.

Figure 1. Important concepts in circulatory support. CPO = cardiac power product; LVEDP = left ventricular end-diastolic pressure; LVESP = left ventricular end-systolic pressure

Typically, in high-risk PCI, we are concerned about creating a vicious cycle of myocardial ischemia with resultant loss of coronary perfusion pressure and then reduction in CPO, leading to further loss of perfusion pressure and more reduction in CPO (Figure 2). This phase may happen when CPO becomes less than <0.6, the point where reduced systemic circulation leads to reduced coronary perfusion. If this continues, a point can be reached where CPO becomes <0.53, beyond which the spiral may be irreversible and tragically end in death. Patients with already-reduced CO and MBP, for example, those with heart failure (HF) or low ejection fraction (EF), frequently require measures that increase CO and MBP.

Figure 2. The vicious cycle of myocardial perfusion, ischemia, and CPO. CPO = cardiac power product; EF = ejection fraction; HF = heart failure; MBP = mean arterial blood pressure

Gaps in current knowledge

Our gaps in knowledge center around understanding which patients are “high-risk,” which device is best suited to which patient, and when (the timing) of mechanical circulatory support (MCS) is appropriate. Additionally, we need to differentiate between patients who suffer predominantly from inadequate coronary circulation, for example a sole surviving coronary artery or left main disease but with normal LV function, and those patients who have both severe coronary disease and hemodynamic compromise. The choice and timing of MCS will differ accordingly.

Figure 3. Currently available mechanical circulatory support devices. CPO = cardiac power product; ECMO = extracorporeal membrane oxygenation; IABP = intraaortic balloon pump; MBP = mean arterial blood pressure.

Possible solutions and future directions

It will be important to develop an individual risk profile for each patient. Broadly speaking, we might consider this to consist of coronary anatomic risk for the PCI procedure, and then in addition consider risk associated with overall patient complexity (Figure 4). There can be high-risk anatomy, but in a low-risk patient, because circulation is okay (normal LVEF). Or, there can be high-risk anatomy in a high-risk patient. Finally, there can be low-risk anatomy, but in a high-risk patient, perhaps because of comorbidities or markedly reduced LVEF. Developing an individual decision aid algorithm which incorporates all these data to help determine whether any MCS is required at all, and if so, which one, is crucial.

Figure 4. Concepts of anatomic risk and patient risk.

In the future, as we refine these concepts and learn more about device characteristics and how to match them to patient risk, we can expect much smoother PCI procedures for the complex, high-risk patients. Furthermore, better left ventricular assist devices will be developed, like a miniaturized percutaneously delivered artificial heart which would completely support the systemic circulation, perhaps even allowing interventional procedures to be done with greater precision and at complete leisure. I will end with a diagram of the vicious cycle of ischemia-coronary perfusion-CPO and indicate some potential points where various available MCS devices might be employed (Figure 5).

Figure 5. Points of intervention with MCS devices. CPO = cardiac power product; MBP = mean arterial blood pressure

References

1. Mishra S, Chiu W, Wolfram R. Role of prophylactic intra-aortic balloon pump in high-risk patients undergoing percutaneous coronary intervention. Am J Cardiol. 2006;98(5):608-612. doi: 10.1016/j.amjcard.2006.03.036. PMID: 16923445.
2. Naidu SS. Novel percutaneous cardiac assist devices. The science of and indications for hemodynamic support. Circulation. 2011;123(5):533-543. doi: 10.1161/CIRCULATIONAHA.110.945055. PMID: 21300961.
3. Mishra S. Upscaling cardiac assist devices in decompensated heart failure: choice of device and its timing. Indian Heart J. 2016;68 (Suppl 1):S1-4. doi: 10.1016/j.ihj.2015.12.012. PMID: 27056646.

7.2       Circulatory Support for Cardiogenic Shock: Matching the Device Strategy to the Patient for Best Outcomes.

Problem Presenter:   Michael Rinaldi, MD

Statement of the problem or issue

Cardiogenic shock (CS) is increasing; the incidence has doubled for patients with acute myocardial infarction (AMI) and those with heart failure (HF). Mortality has not changed despite advances in technology; only ≈50% of patients with CS survive to discharge. CS as a complication of MI or HF is heterogenous, and outcomes depend on clinical phenotype and severity. Clinical (hemodynamic) phenotype is specified as predominantly left sided (LV HF-CS), right sided (RV HF-CS), or both (Bi-V HF-CS). Severity is based on the SCAI-Cardiogenic Shock Working Group (SCAI-CSWG) classification, which has 5 stages: A, B, C, D, E. Other specifications include acuity versus chronicity, and whether the cause is reversible or not. Management requires a right heart cath (RHC) with hemodynamic assessment and phenotyping; any mortality benefit depends on this evaluation. Temporary mechanical circulatory support (tMCS) can be employed for CS; excellent reviews of the topic have been published.¹ Several devices are available (Table 1).

Table 1. Devices for temporary hemodynamic support (tMCS). IABP = intra-aortic balloon pump; LVAD = left ventricular assist device; RVAD = right ventricular assist device; VA-ECMO = veno-arterial extracorporeal membrane oxygenation.

Most algorithms for MCS selection for AMI with CS, and the one we use at my institution, start with Impella CP and then escalate to ECMO as required. And typically, with ECMO, we vent the LV either with Impella (abbreviated EcPella), IABP, or with trans-septal placement of an LA cannula drain (abbreviated LAVA). For patients with HF-CS that is early stage, we start with an Impella CP. But, for patients with Stage C or greater, ECMO with LV venting provides the needed support. Isolated RV shock requires Impella RP; for biventricular support we use ECMO and an LV vent. It is critical to recognize that benefit from mechanical therapies for shock comes not just from improving perfusion with augmentation of cardiac index, but also the hemodynamic support allows more aggressive venous decongestion through diuresis. Venous congestion leads to renal and hepatic failure and a metabolic spiral downward. Rapid and early support can prevent or reverse metabolic derangements that lead to irreversible decline. Importantly, though, mechanical devices are associated with complications including major bleeding and hemolysis and should only be continued as long as necessary. The strategy is to decongest the venous circulation as rapidly as feasible, while simultaneously reversing any reversible causes of shock or supporting the patient through the transient decompensation.

Gaps in current knowledge

Until the recent publication of the DanGer Shock trial showed survival benefit with use of Impella in AMI shock, there was no proven mortality benefit with any device therapy.²    Nevertheless, additional studies are needed to examine benefits of combination therapy, including ECMO with LV venting in severe shock, strategies for non-AMI severe shock, and RV and BiV shock. A consideration of major importance is a de-escalation plan to wean off MCS. Differences in outcomes may reflect how de-escalation was carried out. The goal is to use support only as long as necessary. Continuous re-assessment is required. When congestion has cleared, the RV and end organs have recovered, and cardiac index (CI) on stable pressor doses is maintained, then weaning from MCS can be tested: If successful – decannulate. For patients stabilized using femoral MCS that can’t quickly be weaned, a transition to axillary support may permit extubation and ambulation.

Possible solutions and future directions

There are many unanswered questions that help determine future directions in this field. Some of these are listed in Table 2.

Table 2. Current unanswered questions and future directions.

Future innovations will include lower profile devices, higher flow, greater durability, and even fully implantable devices (Figure).

Figure. Low profile circulatory support devices.

References

1. Narang N, Blumer V, Jumean MF, et al. Management of heart failure-related cardiogenic shock: Practical guidance for clinicians. JACC Heart Fail. 2023;11(7):845-851. doi: 10.1016/j.jchf.2023.04.010. PMID: 37204365.
2. Möller JE, Engstrøm T, Jensen LO, Eiskjær H, Mangner N, Polzin A, et al. Microaxial flow pump or standard care in infarct-related cardiogenic shock. N Engl J Med. 2024;390(15):1382-1393. doi: 10.1056/NEJMoa2312572. PMID: 38587239.

7.3       Novel Devices and New Strategies for the Management of High-Risk Pulmonary Embolism

Problem Presenter:   Souheil Saddekni, MD

Statement of the problem or issue

Pulmonary embolism (PE) is a serious disease, and overall mortality is high. So, we have to treat it seriously. The first step is diagnosis and clinical evaluation. The CT pulmonary angiogram is the greatest diagnostic aid that has come along to help us. But, in addition, there are clinical items we need to evaluate in order to decide how serious a pulmonary embolism may be, and the associated risks, and whether we should treat it aggressively and invasively or with medications only. There are tools which can help us with these assessments.^1-4

Gaps in current knowledge

Although there are several algorithms covering the approach to diagnosis, risk stratification, and treatment of PE, they are all rather complicated. We do not have an “ideal” algorithm. Fundamentally, the two basic choices are (1) a medical therapy approach which can involve fibrinolytic agents and anticoagulation; (2) an invasive approach which can involve catheter-based therapies such as fibrinolysis, mechanical aspiration, or combinations of both. There are many catheter-based devices, and, as of yet there are no studies demonstrating superiority for one or more of them.

Possible solutions and future directions

Many institutions have created pulmonary embolism response teams (PERT). These teams typically are multidisciplinary and include combined interventional cardiology, interventional radiology, cardiac surgery, critical care, and cardiac imaging. PERT teams can help determine risk and help guide therapy. Ongoing developments to produce lower profile catheters with improved efficacy are slowly shifting the emphasis to more catheter-based interventions.

References

1. van Belle A, Büller HR, Huisman MV, et al. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006;295(2):172-179. doi: 10.1001/jama.295.2.172. PMID: 16403929.
2. Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005;172(8):1041-1046. doi: 10.1164/rccm.200506-862OC. PMID: 16020800.
3. Jiménez D, Aujesky D, Moores L, et al. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med. 2010;170(15):1383-1389. doi: 10.1001/archinternmed.2010.199. PMID: 20696966.
4. Hull RD, Raskob GE, Rosenbloom D, Panju AA, Brill-Edwards P, Ginsberg JS, et al. Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis. N Engl J Med. 1990;322(18):1260-1264. doi: 10.1056/NEJM199005033221802. PMID: 2183055.

Session 8: Endovascular Session 2

8.1       Ultrasound Imaging for Endovascular Interventions: A New Standard?

Problem Presenter:   Herbert Aronow, MD

Statement of the problem or issue

Endovascular interventions have been performed for more than 60 years and intravascular ultrasound (IVUS) for more than 40 years, and yet for some reason IVUS is infrequently used for procedural support here. Advantages of IVUS over standalone angiography during endovascular interventions are presented in Table 1.

Table 1. Advantages of IVUS in endovascular interventions. Ca++ = calcium/calcification; MLA = minimal lumen area

There are robust data that IVUS improves clinical outcomes in percutaneous coronary interventions (PCI). What about in endovascular interventions? In a comprehensive meta-analysis of 16 randomized trials with 7814 patients, with weighted mean follow-up of more than 2 years (28.8 months), incorporation of IVUS led to lower risk of major adverse cardiac events (MACE, RR=0.67, P<.001), including cardiac death (RR=0.49, P<.001), stent thrombosis (RR=0.63, P=.046), and target-lesion revascularization (TLR, RR=0.67, P=.01).¹ But is the same true for endovascular interventions? There are much fewer supportive data in the endovascular area, but evidence is accumulating. In a randomized trial of 150 patients undergoing femoropopliteal intervention there was a very significant reduction in the primary endpoint, binary restenosis at 12 months, favoring IVUS over angiography alone (Figure 1).²

Figure 1. Restenosis after femoropoliteal intervention. From: JACC Cardiovasc Interv. 2022;15(5):536-546.

There are also non-randomized, propensity-matched, observational data. In a large study of over a half million patients from 2016 to 2019, there were fewer adverse limb events, lower incidence of acute limb ischemia, and fewer major amputations when IVUS was employed during peripheral vascular interventions rather than angiography alone (Figure 2).³

Figure 2. Adverse events with peripheral vascular interventions. Abbreviations: ALI = acute limb ischemia; MALE = major adverse limb events; NNT = number needed to treat. From: JACC Cardiovasc Interv. 2022;15(20)­:2080-2090.

Gaps in current knowledge

Despite the above data, the overall use of IVUS to support peripheral endovascular interventions in clinical practice is low. In the study cited above, the rates of IVUS use varied by operator specialty, with interventional radiologists having the highest use, followed by cardiologists, surgeons and other specialists (Figure 3).³ Further, while the rate of IVUS use in peripheral endovascular interventions increased over time, on average it was used in fewer than 1 in 8 cases.

Figure 3. Use of IVUS in peripheral vascular interventions, quarterly data, 2016-2019. From: JACC Cardiovasc Interv. 2022;15(20)­:2080-2090.

Possible solutions and future directions

Barriers to greater IVUS use and potential solutions to overcome these are shown in Table 2.

Table 2.  Reasons for low IVUS use and possible steps to close the gap.

Understanding which of these barriers are predominant at your own hospitals will help operators devise site-specific approaches to overcoming these roadblocks.

References

1. Sreenivasan J, Reddy RK, Jamil Y, et al. Intravascular imaging-guided versus angiography-guided percutaneous coronary intervention: A systematic review and meta-analysis of randomized trials. J Am Heart Assoc. 2024;13(2):e031111. doi: 10.1161/JAHA.123.031111. PMID: 38214263.
2. Allan RB, Puckridge PJ, Spark JI, Delaney CL. The impact of intravascular ultrasound on femoropopliteal artery endovascular interventions: A randomized controlled trial. JACC Cardiovasc Interv. 2022;15(5):536-546. doi: 10.1016/j.jcin.2022.01.001. PMID: 35272779.
3. Divakaran S, Parikh SA, Hawkins BM, et al. Temporal trends, practice variation, and associated outcomes with IVUS use during peripheral arterial intervention. JACC Cardiovasc Interv. 2022;15(20):2080-2090. doi: 10.1016/j.jcin.2022.07.050. PMID: 36265940.

8.2       Bioresorbable Scaffolds for BTK Interventions: Are They the Answer or Just Another “Hail Mary”?

Problem Presenter:   George Adams, MD

Statement of the problem or issue

The reason we perform interventions below the knee (BTK) is not only to decrease morbidity, but also to save lives. If you examine the mortality rates of patients with critical limb ischemia (CLI), they are worse than patients with prostate cancer, breast cancer, heart disease, and stroke. Overall, the 1-year mortality rate for patients with CLI is approximately 40-to-50%. This is partly due to the fact that 70% of patients with CLI also have significant coronary disease, and 30% have significant cerebrovascular disease.

Below the knee, the arteries are small vessels, and if you look at treatment modalities, the gold standard is balloon angioplasty (POBA); it is what we compare everything against. The greatest limitation with POBA here is recurrence due to neointimal hyperplasia, or, perhaps, elastic recoil and neointimal hyperplasia. So, the treatment goals are to inhibit or overcome both elastic recoil and neointimal hyperplasia. Both bare metal stents (BMS) and drug eluting stents (DES) have failed in this comparison to POBA. The reason seems to be the remaining mass of metal (the stent) in these small arteries induces such a strong proliferative response that it is difficult or impossible to overcome. These findings have given rise to the strategy of “leave nothing behind.” Presently, this strategy is accomplished by using drug-coated balloons (DCBs), which apply both an expansive dilating force to the lesion as well as deposit an anti-proliferative drug into both the lesion and the adjacent arterial wall. The antiproliferative agent paclitaxel has been used for DCB trials to date. Unfortunately, both DES and DCB trials using paclitaxel BTK have failed.

Gaps in current knowledge

We lack some of the fundamental biologic science that might help devise better treatment strategies. While the “leave nothing behind” strategy appears to be the correct approach, we are still lacking essential basic information regarding DCBs as a method to achieve this. What are the appropriate drug concentrations to place onto DCBs? How long should the balloons be inflated to best deliver drug therapy? Are multiple brief inflations equivalent to one long inflation? What tissue concentrations of drug are needed in the arterial media and adventitia to inhibit hyperplasia? How can we overcome calcification? Can lithoplasty be employed along with DCBs in calcified lesions? These and many other questions require answers.

Possible solutions and future directions

One important group of devices under development are the drug-eluting resorbable scaffolds (DRS). These devices deliver antiproliferative drug to the lesion and arterial wall as they slowly degrade and disappear, leaving “nothing behind.” In addition to these new devices, there is a great deal being learned about optimizing the procedure itself in BTK interventions. This includes vessel and lesion preparation, as well as imaging before, during, and after the procedure. In combination with appropriate biologics and the right strategy, these steps should help improve clinical outcomes in these unfortunate patients.

8.3       BEST Approaches to Revascularization in Critical Limb Ischemia: Interventional or Surgical?

Problem Presenter:   Eric Dippel, MD

Statement of the problem or issue

Therapies for patients with peripheral arterial disease (PAD) and critical limb ischemia (CLI) have not advanced as much as they have for coronary and structural heart diseases. We are far behind in the PAD area. There is too much primary amputation performed for CLI, without adequate evaluation or consideration for revascularization which could salvage 90% of the limbs. The 1-year mortality after major amputation is 40%. Some background is shown in Table 1.

Table 1. Background for Peripheral Arterial Disease and Critical Limb Ischemia. CLI = Critical Limb Ischemia

One of the greatest impediments is interventional treatment of claudication due to PAD; it is not covered at all or is not covered adequately by insurance plans. Can you imagine what it would be like if a woman came into the office and was found to have Stage 1 breast cancer, and she was told “Sorry, we can’t treat you. Not sick enough. Come back when you have Stage 4 breast cancer, and we can treat you then.”

Table 2. Aspects of Problems in Peripheral Arterial Disease and Critical Limb Ischemia.

Gaps in current knowledge

We do not know what treatment is best for which patients with PAD and CLI. There were two randomized trials published within the past year that were supposed to provide insight into this issue. These were the BEST-CLI trial, published in the New England Journal of Medicine, and the BASIL-2 trial, published in Lancet.^1,2 Unfortunately, the way the trials were conducted, using different populations and different primary endpoints, and the fact they reached diametrically opposite conclusions, makes them extremely difficult or impossible to interpret and apply practically. These trials have not answered any questions or solved any problems, they have only created more.

Possible solutions and future directions

We should create dedicated CLI centers of excellence to address some of these problems. We need more rigorous physician training and education. Current fellowships do not adequately address CLI. We should somehow incorporate artificial intelligence into wound healing therapies. Wound treatment is completely non-standardized and haphazard. Further, I would like to see more interdisciplinary cooperation, but that may be difficult to achieve with turf wars so common. The endovascular-oriented societies should take a stronger stance in this. Current interventional cardiology fellows have strong preferences for structural heart training, and not for peripheral arterial system training. They also tend to concentrate on coronary artery disease (Table 3).

Table 3. Possible solutions and future directions.

References

1. Farber A, Menard MT, Conte MS, et al. Surgery or endovascular therapy for chronic limb-threatening ischemia. N Engl J Med. 2022;387(25):2305-2316. doi: 10.1056/NEJMoa2207899. PMID: 36342173.
2. Bradbury AW, Moakes CA, Popplewell M, et al. A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial. Lancet. 2023;401(10390):1798-1809. doi: 10.1016/S0140-6736(23)00462-2. PMID: 37116524.

Session 9: Emerging Therapies Session 1

9.1       Integration of UHD and 3D Interventional Imaging

Problem Presenter:   Richard Smalling, MD, PhD

Statement of the problem or issue

Complex interventional procedures have become the norm for many operators. For example, interventions on bifurcations or chronic total occlusions (CTOs). Even ‘simple’ procedures are not always straightforward. Furthermore, in many situations, the target vessels are now much smaller than in the past. The tools that are available are more intricate, e.g. highly specialized wires, microcatheters, small balloons, etc. Standard angiography alone is limited in several ways, especially in magnification. Previous efforts to deal with these limitations have included pre-procedural imaging for planning purposes (e.g. CT angiograms), adjunctive intraprocedural imaging using IVUS or OCT, and tools for physiologic evaluation (FFR, etc.). However, these alternatives also have limitations. Another possibility is ultra-high-definition angiographic imaging, or ultra-magnification fluoroscopy.

Gaps in current knowledge

We must seek to understand what types of procedures might benefit from high resolution imaging. If used, will it lead to improved procedural performance and clinical outcomes? Are there any increased risks associated with it?

Possible solutions and future directions

Canon Medical Systems has developed a high-definition x-ray imaging technology called HD-76, originally designed for interventional neurosurgical procedures. As illustrated in Figure 1, conventional flat-panel detector imaging can resolve to approximately 194 microns, while the HD-76 system can resolve to 76 microns. It is an “angiographic microscope,” and, importantly, there is no radiation dose penalty for this higher resolution.

Figure 1. Ultra-high-definition imaging.

This new imaging technology has now been released for use more broadly. At our institution, it is being used in complex coronary CTO interventions, as well as in selected peripheral arterial interventions. For example, Figure 2 illustrates a case of a patient with advanced scleroderma and severe vascular reaction of the hands, with ischemic ulcerations of a fingertip. The HD-76 ultra-high-definition imaging system facilitated an interventional procedure to restore blood flow to the ischemic digit and permit healing.

Figure 2. Ultra-high definition imaging facilitated interventional procedure in extremely small vessel of hand.

In addition to ultra-high-definition imaging, there is also the ongoing development of hybrid imaging systems, combining 3D-CT with fluoroscopy to improve and enhance intraprocedural imaging, especially in structural heart disease.³ In particular, transcatheter repair and replacement procedures on the aortic, mitral, and tricuspid valves, and LAAO procedures, may benefit from this combination of imaging modalities.

References

1. Setlur Nagesh SV, Vakharia K, Waqas M, et al. High-definition zoom mode: A high resolution X-ray microscope for neurointerventional treatment procedures. J Neuroimaging. 2019;29(5):565-572. doi: 10.1111/jon.12652. PMID: 31339613.
2. Arain SA, Napierkowski S, Schechter M, Aman W, Smalling RW. Initial experience using a novel high definition (HiDef) imaging system in peripheral arterial interventions. Catheter Cardiovasc Interv. 2020;95 (Supplement S2): S115.
3. Brouwer J, Ten Berg JM, Rensing BJWM, Swaans MJ. First use of futuristic image fusion technology during transcatheter aortic valve replacement. JACC Cardiovasc Interv. 2019;12(21):2223-2224. doi: 10.1016/j.jcin.2019.06.047. PMID: 31377270.

9.2       Renal Denervation: Comparison of Latest Therapeutic Approaches and Indications. Do We Need AUC Criteria?

Problem Presenter:   Dmitriy Feldman, MD

Statement of the problem or issue

Chronically high blood pressure (hypertension, HTN) leads to a vicious cascade of unfavorable pathophysiological changes, from atherosclerotic disease of blood vessels, left ventricular hypertrophy (LVH) and cardiomyopathy, to adverse cardiovascular events such as MI, CHF, and arrhythmias. Similarly, there are a number of adverse effects on the cerebrovascular and peripheral vascular systems as well. The global effects of HTN are tremendous, partly due to its high prevalence and partly due to its role as one of the greatest contributing risk factors to mortality. Nearly 30% of adults worldwide and ~50% of adults in the United States (US) currently suffer from hypertension. Importantly, adequate HTN control has plateaued at 50%, with half of the US population sub-optimally treated. One of the challenges of HTN therapy is poor medication adherence, with 30%-50% of patients non-adherent to HTN medications, even in clinical trials and registries. Importantly, even small consistent reductions in blood pressure (BP) of 10mmHg over time result in ~20% relative risk reduction of major cardiovascular and cerebrovascular events, providing support for guidelines to lower blood pressure to less than 130 mm Hg.

The concept of inactivating renal nerves is not novel; surgical resection of thoracolumbar sympathetic nerves was described as early as the 1930s. In the 1950s, a large study of over 1,200 patients undergoing surgical sympathectomy was published. Interestingly, surgical sympathectomy resulted in inconsistent reductions in BP, but, in those patients that achieved lower BP, there was a long-term mortality benefit. Unfortunately, surgical denervation of the lower body resulted in significant morbidity, including orthostatic hypotension, as well as bowel and bladder dysfunction. Sympathectomy as a treatment for HTN became extinct once medical management of HTN became the standard of care. More recently, the idea of performing percutaneous renal denervation without any adverse effects has resurfaced in the last 2 decades due to technological developments. Renal nerves are located in the adventitial fat layers within 3-5mm from the endoluminal space of the renal arteries. This proximity makes denervation or inactivation of renal nerves (RDN) from within the lumen of the renal arteries a target for endovascular therapies using radiofrequency (RF) energy, high-intensity ultrasound, or alcohol injection (Figure). RDN reduces renal tissue norepinephrine release and “spillover,” reduces muscle sympathetic nerve activity, decreases plasma renin levels, and increases renal plasma flow.

Figure. Renal denervation using radiofrequency (RF) energy or high-intensity ultrasound.

Gaps in current knowledge

Early trials (i.e. Symplicity HTN-3) failed to demonstrate efficacy of RDN in patients with resistant HTN. Since then, a second group of sham-controlled randomized clinical trials (RCTs), in patients with and without medication therapy, have demonstrated consistent but modest reductions in systolic, diastolic, and 24-hr average BP, and also confirmed the safety of RDN. Consistent BP reductions have been observed for up to 3 years of follow-up. Interestingly, treatment of both the main branch along with the distal branches of the renal artery has resulted in larger BP reductions when compared to treating the main branch only. These collective data led the Food and Drug Administration (FDA) in November 2023 to approve both ultrasound- and RFA-based renal denervation devices.

Several gaps remain in our knowledge of RDN therapy, mostly related to its short- and long-term efficacy, patient selection criteria, and identification of responders and non-responders:

1. Who are the best candidates for RDN (clinical characteristics, biomarkers, hemodynamic parameters) and what evaluations are needed prior to referral for RDN?
2. What is the explanation for non-responders (~10-30%) and can we identify pre-procedural predictors of responsiveness to RDN?
3. Can we develop tests/technologies to measure baseline sympathetic activity and then validate the extent of peri-procedural denervation?
4. Do we need to demonstrate importance of reducing end-organ effects and long-term cardiovascular benefits after RDN?
5. What are comparative outcomes between RFA, ultrasound, and alcohol-based technologies?
6. Should we investigate collateral beneficial effects of RDN in other areas (glucose/insulin sensitivity, obstructive sleep apnea, CKD, diastolic heart failure, arrythmias (e.g. atrial fibrillation, ventricular tachycardia)?

Possible solutions and future directions

Serum biomarkers identifying candidates with hyperactive renal sympathetic nervous activity need to be examined, and novel biochemical assays should be developed to predict responsiveness to RDN. Only a high baseline BP has been identified so far as a consistent predictor for treatment responsiveness to RDN. It is important to identify and ensure the completeness of denervation during the procedure itself if possible. In sheep models, pacing the aortic ganglia on each side results in BP increase and ipsilateral renal vasoconstriction, whereas denervation results in abolition of these responses. Peri-procedural nerve stimulation may be used in the future to guide the completeness of RDN and to predict BP response to RDN. Further investigations into potential beneficial effects on several conditions beyond hypertension (glucose/insulin sensitivity, sleep apnea, CKD, diastolic HF, arrythmias) need to be studied. Future devices should include lower profile systems, dedicated catheter devices for transradial procedures and a single device for performing bilateral RDN. Professional society guidelines will be important to avoid RDN overutilization (or underutilization), while focusing on appropriate patient selection, pre-procedural evaluation, strict operator training standards and institutional/facility requirements.^1,2,3 Future development of appropriate use criteria for RDN procedures may be needed once the technology matures.

References

1. Kandzari DE, Townsend RR, Bakris G, et al. Renal denervation in hypertension patients: Proceedings from an expert consensus roundtable cosponsored by SCAI and NKF. Catheter Cardiovasc Interv. 2021;98(3):416-426. doi: 10.1002/ccd.29884 PMID: 34343406.
2. Swaminathan RV, East CA, Feldman DN, et al. SCAI position statement on renal denervation for hypertension: Patient selection, operator competence, training and techniques, and organizational recommendations. JSCAI 2023;2(6):101121. doi: 10.1016/j.jscai.2023.101121
3. Barbato E, Azizi M, Schmieder RE, et al. Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2023;44(15):1313-1330. doi: 10.1093/eurheartj/ehad054. Erratum in: Eur Heart J. 2023 Jul 14;44(27):2439. PMID: 36790101.

9.3       Bio-Resorbable Scaffolds: What is their Future?

Problem Presenter:   Sundeep Mishra, MD

Statement of the problem or issue

Metallic stents have certain limitations. For example, there are technical issues and difficulties with placing them in angulated and tortuous vessels, delivering longer stents around bends, or positioning them in vein grafts. Metallic stents have rates of restenosis of up to 5%, stent thrombosis in 0.5%-1%, and stress fracture rates of 1%-8%. Metallic stents may impede or even prevent CABG if too many are placed into far distal sections of coronary arteries, thereby precluding vein graft attachment. Attempts to overcome these limitations led to the development of bioresorbable vascular scaffolds (BVS), stent-like devices that dissolve away slowly over months. The last sizable BVS study was ABSORB III.¹ Unfortunately, long-term results were not favorable. Late-lumen loss was greater with BVS, and TLR, target vessel MI, and very-late scaffold thrombosis rates all were higher with it.²

Gaps in current knowledge

There is incomplete understanding why BVS are inadequate when theoretically they should be superior. Some of these knowledge gaps areas are listed in the Table. Lower radial strength with BVS, which is logarithmically less than metallic stents, seems to be the prime reason for their lack of superiority, contributing to greater mal-apposition and inadequate embedment in the vessel wall. Their greater strut thickness does not overcome this limitation.^3,4 Bioresorbable metallic stents, like those composed of magnesium alloys, do have greater radial strength but still are only a partial solution since they degrade and are resorbed relatively quickly.

Table. Knowledge gap areas for bioresorbable vascular scaffolds.

Possible solutions and future directions

A number of initiatives are underway to overcome BVS limitations. The correct procedural techniques, including use of intravascular imaging, are under investigation. Strut materials and coatings are being developed and examined. Physical and mechanical properties of BVS are being scrutinized, especially radial strength.⁵ The current challenge is how to increase the radial strength of the polymer to bring it closer to that of a metal. For magnesium alloy stents the improved polymer coatings may slow the degradation/resorption process and permit adequate and sustained drug delivery. Newer iron or zinc alloys or a hybrid metallic-polymer material may provide another solution.

References

1. Wykrzykowska JJ, Kraak RP, Hofma SH, et al. Bioresorbable scaffolds versus metallic stents in routine PCI. N Engl J Med. 2017;376(24):2319-2328. doi: 10.1056/NEJMoa1614954. PMID: 28402237.
2. Kereiakes DJ, Ellis SG, Metzger DC, et al. Clinical outcomes before and after complete everolimus-eluting bioresorbable scaffold resorption: Five-year follow-up from the ABSORB III trial. Circulation. 2019;140(23):1895-1903. doi: 10.1161/CIRCULATIONAHA.119.042584. PMID: 31553222.
3. Mishra S. Bioresorbable scaffold -fourth revolution or failed revolution: Is low scaffold strut thickness the wrong target? Indian Heart J. 2017;69(6):687-689. doi: 10.1016/j.ihj.2017.10.004. PMID: 29174242.
4. Mishra S. Structural and design evolution of bio-resorbable scaffolds: The journey so far. Curr Pharm Des. 2018;24(4):402-413. doi: 10.2174/1381612824666171227212737. PMID: 29283053.
5. Mishra S. A fresh look at bioresorbable scaffold technology: Intuition pumps. Indian Heart J. 2017;69(1):107-111. doi: 10.1016/j.ihj.2017.01.006. PMID: 28228292.

Session 10: Coronary Session 3

10.1     Invasive vs. Noninvasive Coronary Lesion Physiology: Who Should Get What and in Which Settings

Problem Presenter:   Kirk Garrett, MD

Statement of the problem or issue

Noninvasive coronary physiology based on CT-FFR (computed tomography fractional flow reserve) has much to recommend it. However, the value proposition of it is still evolving. It may have the potential to offer some efficiencies in the way we use invasive services, since it is a non-invasive imaging modality that can give us both anatomic and physiologic information. The PRECISE trial tested the hypothesis of whether CT-FFR, combined with risk stratification (that is, a clinical risk tool), could substitute for our traditional approach to non-invasive evaluation of patients with stable coronary disease.^1,2 It turned out there were benefits seen with this PRECISE, or rather, PRECISION strategy. The greatest benefit was in reducing invasive services in patients who turned out to have mild or no coronary disease that needed treatment beyond medical therapies. There is also a similar, related analytic process that uses standard angiograms coupled with proprietary software to reconstruct the vessel and its territory, and then apply fluid dynamics equations to calculate another parameter called the Quantitative Flow Ratio (QFR).^3,4 The QFR may discriminate between significant and nonsignificant coronary lesions, similar to FFR.

Gaps in current knowledge

The most compelling thing about CT-FFR, although still unproven, may be in the ability to use our cath labs more efficiently. In the PRECISE trial, patients in the standard care arm underwent evaluations, and ultimately 17% required coronary angiograms. In the precision care arm, with CT-FFR employed, only 13% required angiograms. But, importantly, a higher proportion of patients in the precision care arm required revascularization with PCI compared to the standard care arm (7.3% vs 3.5%), since the CT-FFR testing helped eliminate those patients unlikely to have obstructive coronary disease. Based on the financial estimates, there was approximately 20% more revenue per 100 patients undergoing coronary angiograms in the precision group compared to the standard care group. Therefore, the hypothesis is that the more accurate screening in the precision arm might make cath labs more efficient.

Possible solutions and future directions

Both of these methodologies, CT-FFR and QFR, will undergo rigorous testing and examination in the next few years. Clinical outcomes data demonstrating superiority for either of them over and above current practices have not yet been accumulated. The value proposition also still needs to be proven or refuted: Do either of these technologies make our invasive cath labs more operationally efficient?

References

1. Douglas PS, Nanna MG, Kelsey MD, et al. Comparison of an initial risk-based testing strategy vs usual testing in stable symptomatic patients with suspected coronary artery disease: The PRECISE randomized clinical trial. JAMA Cardiol. 2023;8(10):904-914. doi: 10.1001/jamacardio.2023.2595. PMID: 37610731.
2. Udelson JE, Kelsey MD, Nanna MG, et al. Deferred testing in stable outpatients with suspected coronary artery disease: A prespecified secondary analysis of the PRECISE randomized clinical trial. JAMA Cardiol. 2023;8(10):915-924. doi: 10.1001/jamacardio.2023.2614. PMID: 37610768.
3. Tu S, Westra J, Adjedj J, et al. Fractional flow reserve in clinical practice: from wire-based invasive measurement to image-based computation. Eur Heart J. 2020;41(34):3271-3279. doi: 10.1093/eurheartj/ehz918. PMID: 31886479.
4. Kanno Y, Hoshino M, Hamaya R, et al. Functional classification discordance in intermediate coronary stenoses between fractional flow reserve and angiography-based quantitative flow ratio. Open Heart. 2020;7(1):e001179. doi: 10.1136/openhrt-2019-001179. PMID: 32076563.

10.2     A Critical Appraisal of Intravascular Imaging: When Does It Really Matter?

Problem Presenter:   Alexander Truesdell, MD

Statement of the problem or issue

The evidence base for intravascular imaging (IVI) in percutaneous coronary intervention (PCI) largely consists of trials in complex lesion subsets. There are robust randomized controlled trial and registry data supporting use of IVI to improve clinical outcomes, including cardiac death, target lesion myocardial infarction, and clinically- or ischemia-driven target lesion and vessel revascularization. These data exist for bifurcation lesions, long lesions, severely calcified lesions, left main lesions, ostial lesions, in-stent restenosis, and chronic total occlusions (CTO).^1,2 Thus, in these situations, it is easy to advocate both for routine use of IVI and an accompanying Guidelines upgrade to a 1A indication (from 2A currently). It may be more difficult to advocate for routine IVI in other, non-complex lesions, where the magnitude of benefit may be less. Nevertheless, more frequent, and even routine, use of IVI in PCI can be justified as a “Best Practice,” similar to radial access. Furthermore, routine use of IVI may improve individual and team technical competency, and also shorten procedure times, as IVI is incorporated into standard cardiac catheterization laboratory (CCL) workflow.³ In a comprehensive review of this subject, there were 3 broad areas outlined where IVI can be useful in routine PCI: (1) preintervention assessment; (2) lesion preparation and stent deployment; (3) assessment of postprocedure endpoints and complications.⁴ Details are summarized in Table 1.

Table 1. Intravascular imaging in PCI.

Gaps in current knowledge

The absolute benefit of routine use of IVI in all lesions is unclear. Similarly, the aggregate benefit of IVI as one component of a suite of CCL practices – including radial access, optimal antiplatelet therapy, ultrasound-guidance for vascular access, and physiologic lesion assessment – is also unknown.⁵ To the extent that IVI in PCI is looked upon as a “Best Practice,” the appropriate division of responsibilities to foster greater implementation remains unclear – but probably involves collaborative effort among individual operators, healthcare institutions, and national cardiovascular societies, as outlined in Table 2. Finally, the impact of integration of different invasive and noninvasive multimodality imaging techniques together to detect vulnerable plaque and influence follow-on PCI procedures, implement lifestyle interventions, adjust pharmacologic therapy, and guide lifelong disease prevention and surveillance is also unknown but likely worthwhile.⁶

Table 2. Recommendations for promoting intravascular imaging in PCI.

Possible solutions and future directions

We need to expand the evidence base for IVI from complex lesion subsets to a broader variety of lesions, and ultimately to routine use. It is hoped that as a “Best Practice,” routine use of IVI will lead to better and more complete and successful procedures that ultimately will reduce short-, medium-, and long-term costs by reducing target lesion and target vessel revascularization. Clinical outcomes data and cost issues should continue to be explored. Integrated multimodality imaging – combining multiple imaging technologies in a single device – may also soon be widely available. Industry partners should consider direct integration of IVI into future radiologic systems as part of a modern CCL “cockpit” (which may also include both invasive and noninvasive physiologic and histologic imaging data as standards). IVI data and endpoints should be considered for inclusion in all standard cardiac catheterization reports and NCDR data collection tools. Finally, artificial intelligence (AI) programs can be applied to aid image interpretation, lesion characterization, PCI guidance and endpoint assessment, and additionally can provide real-time and ongoing career-long operator and team education and training.

References

1.         Capodanno D, Spagnolo M. Optical coherence tomography or intravascular ultrasound for complex PCI: Different approaches, similar outcomes. J Am Coll Cardiol. 2024;83(3):414-416. doi: 10.1016/j.jacc.2023.10.044.

2.         Sreenivasan J, Reddy RK, Jamil Y, et al. Intravascular imaging-guided versus angiography-guided percutaneous coronary intervention: A systematic review and meta-analysis of randomized trials. J Am Heart Assoc. 2024;13(2):e031111. Epub 2024 Jan 12. doi: 10.1161/JAHA.123.031111. 

3.         Sung JG, Sharkawi MA, Shah PB, Croce KJ, Bergmark BA. Integrating intracoronary imaging into PCI workflow and catheterization laboratory culture. Current Cardiovascular Imaging Reports. 2021;14:6.

4.         Truesdell AG, Alasnag MA, Kaul P, et al. Intravascular imaging during percutaneous coronary intervention: JACC State-of-the-Art Review. J Am Coll Cardiol. 2023;81(6):590-605. doi: 10.1016/j.jacc.2022.11.045

5.         Khuddus MA, Truesdell AG, Kirtane AJ. Leveraging the power of marginal gains to improve outcomes in interventional cardiology. JAMA Cardiol 2020;5(2):121-123. doi: 10.1001/jamacardio.2019.4278

6.         Li J, Montarello Nicholas J, Hoogendoorn A, et al. Multimodality intravascular imaging of high-risk coronary plaque. JACC: Cardiovascular Imaging 2022;15(1):145-159. Epub 2021 May 19. doi: 10.1016/j.jcmg.2021.03.028. 

10.3     Latest Devices for CTO Intervention: Do They Improve Outcomes and Change Indications?

Problem Presenter:   Rajan Patel, MD

Statement of the problem or issue

The prevalence of chronic total occlusions (CTO) in all patients undergoing coronary angiography is approximately 15%. In patients with acute coronary syndromes, it increases to around 30-to-40%. In patients undergoing coronary angiography who have had previous coronary artery bypass surgery (CABG), the prevalence of a CTO is 50% or more. The benefit of reopening a CTO is quality of life for the patient. There are 4 studies of CTO PCI that demonstrate benefit for quality of life and other symptoms (Table 1).^1-4

Table 1. Benefits of CTO PCI.

The procedural risk for major adverse events in CTO PCI is approximately double that for non-CTO PCI, 1.6% compared to 0.8%.⁵ In a large, comprehensive review of CTO PCI from a decade ago, which included 18,000 patients in 65 studies, the most common complications were coronary perforation, MI, and contrast-induced acute kidney injury.⁶ In the large national registries, CTO PCI overall procedural success rates are approximately 75%, and for registries based at experienced CTO centers, procedural success rates are better at approximately 85%-90%. However, these procedural success rates are lower than success rates in non-CTO PCI, and they help explain why CTO PCI has not caught on more broadly and become a staple coronary procedure.

In terms of devices, there are a number of them available for use in CTO PCI; some are listed in Table 2.

Table 2. Devices for CTO PCI.

There are a few prospective single arm studies examining these devices. However, such studies are of questionable utility. What these devices do is make CTO PCI procedures more consistent, faster, and thereby possibly safer. There is no magic in the devices specifically. Especially when these devices are used as part of an algorithm, they seem to be associated with higher success rates.

Gaps in current knowledge

There are a number of knowledge gaps in CTO PCI. If we are not able to demonstrate a mortality benefit for CTO PCI, which has been almost impossible to do for any PCI except primary PCI for STEMI, then what other metrics can we examine? Several candidates for these alternative metrics where information gaps exist are listed in Table 3.

Table 3. Knowledge and information gaps in CTO PCI.

Possible solutions and future directions

Several important factors appear to have moved this field forward, and likely will continue to do so for the foreseeable future. These factors are listed in Table 4.

Table 4. Important factors driving the CTO PCI field forward.

Finally, the field needs to move forward from hypothesis generating studies to hypothesis testing studies. The available devices coupled with an algorithmic approach, employed by skilled operators at dedicated team-based centers, will be the next phase.

References

1. Olivari Z, Rubartelli P, Piscione F, et al. Immediate results and one-year clinical outcome after percutaneous coronary interventions in chronic total occlusions: data from a multicenter, prospective, observational study (TOAST-GISE). J Am Coll Cardiol. 2003;41(10):1672-1678. doi: 10.1016/s0735-1097(03)00312-7. PMID: 12767645.
2. Christakopoulos GE, Christopoulos G, Carlino M, et al. Meta-analysis of clinical outcomes of patients who underwent percutaneous coronary interventions for chronic total occlusions. Am J Cardiol. 2015;115(10):1367-1375. doi: 10.1016/j.amjcard.2015.02.038. PMID: 25784515.
3. Joyal D, Afilalo J, Rinfret S. Effectiveness of recanalization of chronic total occlusions: a systematic review and meta-analysis. Am Heart J. 2010;160(1):179-187. doi: 10.1016/j.ahj.2010.04.015. PMID: 20598990.
4. Bruckel JT, Jaffer FA, O'Brien C, Stone L, Pomerantsev E, Yeh RW. Angina severity, depression, and response to percutaneous revascularization in patients with chronic total occlusion of coronary arteries. J Invasive Cardiol. 2016;28(2):44-51. PMID: 26477043.
5. Brilakis ES, Banerjee S, Karmpaliotis D, et al. Procedural outcomes of chronic total occlusion percutaneous coronary intervention: a report from the NCDR (National Cardiovascular Data Registry). JACC Cardiovasc Interv. 2015;8(2):245-253. doi: 10.1016/j.jcin.2014.08.014. PMID: 25700746.
6. Patel, V, Brayton, K, Tamayo, A. et al. Angiographic success and procedural complications in patients undergoing percutaneous coronary chronic total occlusion interventions: A weighted meta-analysis of 18,061 patients from 65 studies. JACC Cardiac Interv. 2013;6(2):128-136. doi:/10.1016/j.jcin.2012.10.011.

Session 11: Health Care Delivery Session 1

11.1     Artificial Intelligence in Interventional Medicine

Problem Presenter:   Bonnie Weiner, MD

Statement of the problem or issue

Artificial intelligence (AI) is actually a misnomer; it is more correct to call it augmented intelligence. It has been around for a very long time. A calculator is a form of AI, and we have had mechanical calculators for over 100 years. Nevertheless, the use of AI in medicine, cardiology, and interventional cardiology is increasing, as illustrated by publications on the subject (Figure 1).

Figure 1. Publications referencing AI in interventional cardiology.

Three broad areas of application of AI in medicine are: (1) medical image analysis; (2) genomics analysis; (3) natural language processing. For our practical purposes, it is useful to classify AI uses as listed in Table 1.

Table 1. Practical applications of AI in medicine.

On the topic of imaging, AI may offer the opportunity to have a completely objective analysis rather than a subjective analysis of angiograms, IVUS, and OCT. In fact, part of the underutilization of IVUS and OCT imaging may be that some or many operators are not comfortable interpreting the images. They are comfortable performing the procedures, but less comfortable interpreting the images, and AI may not only provide an educational tool but also increase operator comfort level and use. For many of the other areas, some clinicians are skeptical or hesitant (or downright fearful) of what has come down to them, because the products and systems were forced on them from a purely business-oriented model, or from other components of the healthcare system that either want to make money or streamline their processes at the expense of clinician-led processes. The concern here is that AI may overstep or contradict clinical judgment or test interpretation. None of these concerns would arise if AI is used appropriately.

Gaps in current knowledge

We have enormous gaps in our knowledge base regarding applications of AI in medicine, cardiology, and interventional cardiology. Some aspects are listed in Table 2.

Table 2. Knowledge gap areas.

Possible solutions and future directions

We are only at the very beginning of AI implementation in clinical practice. There is a great deal to learn. However, we must never lose sight of the fact that AI is just a tool, and like all tools it can have good or bad applications. There will always have to be human oversight and engagement. Change is always a challenge, but fear is not a productive response.

References

1. Subhan S, Malik J, Haq AU, et al. Role of artificial intelligence and machine learning in interventional cardiology. Curr Probl Cardiol. 2023;48(7):101698. doi: 10.1016/j.cpcardiol.2023.101698 PMID: 36921654.
2. Singh A, Miller RJH, Otaki Y, et al. Direct risk assessment from myocardial perfusion imaging using explainable deep learning. JACC Cardiovasc Imaging. 2023;16(2):209-220. doi: 10.1016/j.jcmg.2022.07.017 PMID: 36274041.
3. Williams MC, Bednarski BP, Pieszko K, et al. Unsupervised learning to characterize patients with known coronary artery disease undergoing myocardial perfusion imaging. Eur J Nucl Med Mol Imaging. 2023;50(9):2656-2668. Epub 2023 Apr 17. doi: 10.1007/s00259-023-06218-z PMID: 37067586.
4. Rudnicka Z, Pręgowska A, Glądys K, Perkins M, Proniewska K. Advancements in artificial intelligence-driven techniques for interventional cardiology. Cardiol J. 2024;31(2):321-341. Epub 2024 Jan 22. doi: 10.5603/cj.98650. PMID: 38247435

11.2     Health Equity

Problem Presenter:   Sam Conaway, MBA

Statement of the problem or issue

Studies show that patients in minority populations are not accessing specialty care due to barriers in our healthcare system. We have data demonstrating racial and ethnic under-representation in clinical trials, and particularly in cardiovascular clinical trials. It’s not that doctors and caregivers exclude certain patients on purpose; there are many factors involved. Some of it is due to unconscious bias; some of it is trust. There are many people of color who do not go to doctors from a lack of trust. These factors all combine to produce inequality in health care. We are all called to action to work together and close the gaps. There is a famous quote by Martin Luther King: “Of all the forms of inequality, injustice in health care is the most shocking and inhumane.” 

Gaps in current knowledge

For Black patients with peripheral arterial disease (PAD), they are twice as likely to undergo an amputation and less likely to have a revascularization procedure first. For Hispanics, they are 15% less likely to undergo a PCI procedure when presenting with heart attack symptoms. Among patients with atrial fibrillation, if you're a black patient, you account for less than 4% of left atrial appendage closure devices. In patients with heart failure, Black and Hispanic patients are less likely to receive CRT and ICD therapies. Our population is 51% female. Yet, females only represent ≈33% of patients enrolled in clinical trials. African Americans represent ≈14% of the population, yet they represent <7% of patients enrolled in clinical trials. Hispanics represent less than 6% of enrollees in clinical trials. So, we must get more demographically diverse patients engaged in clinical trials in order for them to begin to trust what is going on.

Possible solutions and future directions

At Boston Scientific we started a trial called Platinum Diversity (NCT02240810).¹ One of the myths we dispelled was that enrolling ethnically diverse patients would slow down enrollment. In fact, it was the second fastest enrolling trial in Boston Scientific history. Another myth: It’s hard to find diverse physician investigators (PIs). Well, with Platinum Diversity and the Elegance registry (which is focused on PAD), we not only had outstanding PIs that were a diverse group, but our entire steering committee was diverse, composed of women and people of color.² So, another myth: Diverse patient enrollment will create higher rates of loss to follow-up. Yet, in both of these studies, Platinum and Elegance, rates of loss to follow-up were comparable for minorities and white men. Diverse enrollment is not going to hurt your trial. Final myth for today: Enrollment caps will delay trials, and investigators don’t like them. In Elegance, enrollment caps haven’t delayed the trial at all. It’s a fast-enrolling trial, and we’ve received extremely positive feedback on enrollment caps. And, in addition, we’re doing a trial right now for left atrial appendage closure, and the strategy earlier was to first enroll 500 patients, and then at the 500-patient mark, stop that portion of the trial and switch enrollment to people of color only. We did just that. We plan to enroll 200 additional patients, and we’re enrolling them faster in the 200-patient arm than we did in the 500-patient arm. So, slower trial enrollment from patient caps is just another myth.

References

1. Avaliable at: clintrials.gov/study/NCT02240810. Accessed 01 May 2024.
2. Kohi MP, Secemsky EA, Kirksey L, Greenberg-Worisek AJ, Jaff MR. The ELEGANCE registry: Working to achieve equity in clinical research design. NEJM Catal Innov Care Deliv. 2023;4(8). DOI: 10.1056/CAT.23.0010

11.3     The Consequences of Public Reporting and Star Ratings

Problem Presenter:   Michael Rinaldi, MD

Statement of the problem or issue

Are there any benefits to public reporting (PR) of patient outcomes and ratings (or rankings) of hospital systems? Some proposed benefits are listed in Table 1.

Table 1. Several proposed benefits of public reporting.

While there are certain degrees of transparency achieved with PR, it is not clear that quality is improved. Furthermore, there are unintended consequences with PR, for example through risk avoidance. Studies of bypass surgery (CABG) dating back to the 1980s revealed that reported outcomes improved, but significant risk avoidance contributed to these improvements. In PCI, most in-hospital mortality is related to out-of-hospital cardiac arrest and cardiogenic shock, and not to cardiovascular care patterns.¹ Avoiding the “risks” inherent in these two types of patients might improve reported outcomes, but possibly at the expense of reduced care for the sickest patients. With TAVR, the situation is the same. We now have a TVT-ACC three-star rating system. The outcomes that determine a hospital’s star-rating are largely driven by how aggressively the hospital captures and codes comorbidity codes (MCCs), and those MCCs are almost always related to acute heart failure. And it turns out there is wide variance in the United States with heart failure codes, from <20% in some institutions up to 80% in others. So, differences in outcomes and star-ratings may represent only coding and gaming. Finally, the difference in mortality between the top and bottom quartiles of institutions is <1%; is that really meaningful?

Gaps in current knowledge

Can quality in healthcare actually be measured, and can programs be compared based on those measurements? Can we actually determine whether the data are accurate? In the TVT registry for TAVR, the top 10% of centers report no bleeding, no pacemaker requirement, no vascular complications, and no mortality. Does anyone really believe this, and can audits really police it? And furthermore, do patients and payors care? Patients are generally unaware of public reporting, and they rarely use the information they receive. Patients choose providers based on what is closest to them, word of mouth, and then, where their doctor refers them. Referring physicians don’t use PR either. They refer to their friends and providers who are in their network. Payors generally don’t care either; they are more focused on lower cost, and they are not really basing episodes of care on quality. So, favorable PR does not move market share. U.S. News and World Report ranks programs. STS and ACC have tried to provide context by ranking systems with discrete star ratings, but is this meaningful or fair? Should our professional societies be declaring winners and losers unless there are meaningful differences that are not driven by gaming and avoidance?

Does public reporting of outcomes, and rankings of individual programs, impact patient care negatively? Unfortunately, the answer appears to be ‘Yes’. Public reporting leads to risk avoidance, that is, avoidance of high-risk cases that often are most likely to benefit. Hospital systems operating in underserved communities fare the worst because they have the least resources to play the game.

Possible solutions and future directions

Public reporting is here to stay, and there are some benefits. The public and some patients and patient advocacy groups demand it, even though they may not use the information provided. It offers an illusion of transparency, however cynical that is. Nevertheless, the activity of PR helps encourage quality processes in institutions. That’s good. Public reporting is a good thing for this reason, but let’s not pretend that it’s more than only loosely associated with true quality. Quality measures for individual institutional comparisons I believe are unknowable; what we can observe are average performers versus extreme outliers. If we change from a star rating system perhaps we could mitigate some of the gaming and risk aversion that goes on, trying to chase that additional star. We should emphasize process metrics to drive quality over meaningless outcome metrics. So, instead of reporting mortality rate or bleeding rate, we could report nurse-to-patient ratio, or, nursing retention ratio, or, proportion of 24/7 critical care coverage in your ICU, metrics that will drive institutions toward actual improved quality. We must ensure the use of best practices are encouraged rather than optimization of raw or risk-adjusted outcomes numbers, and not designate institutions as winners or losers, but designate them as either achieving high quality or in need of improvement. We should establish institutional processes that we know improve quality rather than chase “outcomes metrics” that are subject to gaming. Finally, we should encourage our professional societies to change how we rank institutions to oblige them to invest resources in processes that actually save lives and improve quality.

Reference

1. Resnic FS, Majithia A. What death after percutaneous coronary intervention cannot teach. Circ Cardiovasc Qual Outcomes. 2019 May;12(5):e005692. doi: 10.1161/CIRCOUTCOMES.119.005692. PMID: 31104471.