source: tctMD

MitraClip ‘Bridge’ Strategy Continues to Help Sickest HF Patients

With MitraClip, 20% of advanced HF patients awaiting transplant improved enough to no longer require a new heart.

PARIS, France—Two years after undergoing edge-to-edge repair with MitraClip as a bridge to heart transplantation, roughly half of these very sick heart failure (HF) patients received a new heart, became eligible to get one, or no longer required it because their symptoms improved, according to longer-term follow-up from the MitraBridge study.

The new data, which was presented during a late-breaking clinical trial session at EuroPCR 2022, is an update to the 2020 study showing that MitraClip could be an effective bridging strategy for advanced HF patients with secondary mitral regurgitation (MR). At that time, investigators reported that use of MitraClip allowed more than 30% of patients to be safely bridged until a heart became available or their clinical status improved enough to become eligible for transplantation.

Andrea Raffaele Munafò, MD, PhD (University of Pavia, Italy), who presented the updated MitraBridge results, explained the rationale for the bridge treatment.

“In advanced stages of heart failure with reduced ejection fraction, where volume overload and reduced stroke volume play a key role, a significant regurgitant volume might further increase left ventricular end-diastolic pressure and impair stroke volume, [which would] affect the patient’s prognosis,” said Munafò. “The MitraClip treatment might interrupt this maladaptive process and guarantee patients clinical and hemodynamic stabilization and allow safe access to a heart transplantation.”

The bridge strategy included 153 patients who were awaiting transplant but who had a low likelihood of receiving a new heart quickly (bridge to transplant), those not yet listed for transplant because of potentially reversible contraindications (bridge to candidacy), and those with worsening clinical status awaiting a final clinical decision on transplant (bridge to decision).

The 2-year rate of freedom from death, need for urgent heart transplantation or LVAD transplantation, and first hospitalization was 47%. Overall, 55% avoided a first hospitalization during this follow-up period. The annualized rate of HF hospitalization was 45.5% for those who received the device.

Regarding clinical status at 2 years, 19.5% of patients underwent elective transplantation and 12.5% were successfully bridged to eligibility where they were placed on the waiting list. Another 21% of patients no longer required a heart transplantation because of a significant clinical improvement.

Ulrich Schäfer, MD (Marienkrankenhaus Hamburg, Germany), one of the panelists during the session, said there is interest in understanding more about the “responders” who no longer required a transplant because of a clinical improvement. Munafò said further study is needed but noted that these patients tended to have better baseline left ventricular ejection fractions compared with the others.

In terms of baseline echocardiographic characteristics, Munafò said the MitraBridge patients are more closely aligned with patients in MITRA-FR as opposed to the COAPT trial, at least in terms of echocardiographic characteristics at baseline. However, the median age of patients in MITRA-FR was 73 years versus 59 years in MitraBridge, and those included in the registry also had more severely impaired left ventricular function, he said.
e severely impaired left ventricular function, he said.

MitraClip ‘Bridge’ Strategy Continues to Help Sickest HF Patients | tctmd.com

 

Fibromuscular Dysplasia in SCAD Tied to Worse Long-term Prognosis

Up to 80% of those screened have FMD, a systemic disease that doubles the risk of recurrent MI and MACE at 3 years after SCAD.

PARIS, France—For patients with spontaneous coronary artery dissection (SCAD), fibromuscular dysplasia (FMD) independently predicts poorer prognosis over the long term, observational data show.

Within a few years after the initial event, the risks of recurrent MI and overall MACE each were more than doubled among those with the blood-vessel disorder, Jacqueline Saw, MD (Vancouver General Hospital, Canada), reported today at EuroPCR 2022.

“We’re a decade into the journey of trying to create awareness about SCAD,” Saw said in an interview with TCTMD. Thanks to that work, “when a woman presents with MI, especially if they’re younger, middle-aged, and have no other cardiovascular risk factors, SCAD does come into consideration now. Awareness is better.”

Among SCAD specialists, too, there has been growing appreciation of FMD as a risk factor, she said. “We’ve been trying to promote [the idea] that all patients with SCAD should be screened for FMD. But has that translated to real-world practice? Not entirely. I would say that probably still about 60% to 70% of patients with SCAD are actually screened for FMD.”

Saw told EuroPCR attendees that screening, when it does happen, identifies a roughly 50% to 80% prevalence of FMD among SCAD patients, with catheter-based angiography getting a higher yield of positives than CT angiography.

“Typically, we would recommend that you do a three vascular territory screening” in the head and neck as well as in the renal and iliac arteries. If anything, the current report underestimates the prevalence, since it wasn’t mandatory for participating centers to screen all three sites or use a particular screening tool, Saw explained.

No Difference in In-Hospital Outcomes

For the study, Saw and colleagues analyzed data from the Canadian SCAD study, identifying 981 patients who underwent screening for FMD. Among them, 50.5% were found to have FMD.

Compared to those without FMD, patients who got the diagnosis were older (mean 53.9 vs 50.3 years) and had a lower body mass index (mean 25.9 vs 28.0 kg/m²; P < 0.001 for both). They were more likely to be female (94.7% vs 85.8%; P < 0.001), postmenopause (60.0% vs 43.0%; P < 0.001), and currently receiving hormone therapy (11.5% vs 7.6%; P = 0.029). They also were more apt to had intracranial aneurysm (7.7% vs 3.5%; P = 0.005) and hypertension (38.2% vs 31.1%; P = 0.022). Other comorbidities were similar in both groups.

There were no differences in pregnancy history, mode of SCAD presentation, possible SCAD triggers, SCAD vessel location or angiographic appearance, LVEF, or management strategy. In-hospital outcomes also were equivalent between the two groups.

Yet, over a median follow-up of 3.14 years, the SCAD patients with FMD had higher rates of recurrent MI (14.5% vs 7.4%; P < 0.001), SCAD (7.7% vs 4.1%; P = 0.021), revascularization (3.6% vs 1.4%; P = 0.041), and MACE (18.0% vs 9.7%; P < 0.001), a composite that included death, MI, stroke/TIA, hospitalization for heart failure, and unplanned revascularization.

On multivariate analysis, FMD carried significantly increased risks of both recurrent MI (adjusted OR 2.23; 95% CI 1.37-3.63) and MACE (adjusted OR 2.08; 95% CI 1.34-3.24). “Other important variables also included younger age less than 50 and presence of intracranial aneurysm,” Saw noted.

Ran Kornowski, MD (Rabin Medical Center, Petah Tikva, Israel), one of the session’s facilitators, asked how knowing about FMD changes management: “When you diagnose FMD among the SCAD patients, do you treat them differently? Do you do something you would not do otherwise?”

There are no known ways to prevent or treat FMD “in terms of reversing the vascular changes that we see,” Saw replied. “But I think what we can do is try to prevent tears in vascular territories already affected by FMD. For instance, if we identify FMD in the cervical neck, we tell patients they should not participate in high-velocity, impact sports or chiropractic neck manipulation.”

Sex hormones have been implicated in the development of SCAD, since the events tend to occur more often among women, and are a key contributor toward MIs among pregnant women in particular, as a 2020 state-of-the-art review notes. This raises the question, Kornowski noted, of how an FMD diagnosis should affect use of hormone replacement therapy (HRT). Saw said that for all SCAD patients, it’s advised that they not continue taking HRT or oral contraceptives. “Having FMD doesn’t necessarily change that recommendation,” she noted.

Nor does having a diagnosis of FMD change the treatment of SCAD, Saw pointed out to TCTMD. However, knowing that a patient has the systemic condition is a reminder for clinicians to be alert to other problems that might appear elsewhere in their body, such as cerebral aneurysm, and to take steps to prevent injuries.

Fibromuscular Dysplasia in SCAD Tied to Worse Long-term Prognosis | tctmd.com

 

Distal Radial Access Doesn’t Lower Risk of Occlusion: DISCO RADIAL

Although it wasn’t superior to conventional radial access, distal radial was safe and might be a useful option in select cases.

Distal Radial Access Doesn’t Lower Risk of Occlusion: DISCO RADIAL

 

TriCLASP: Tricuspid Repair With Pascal Safe, Effective at 30 days

With many devices in development to treat TR, Edwin Ho says having options will be key in tailoring treatment to anatomy.

PARIS, France—Thirty-day outcomes of the TriCLASP postmarket study of the Pascal and Pascal Ace transcatheter repair systems (Edwards Lifesciences) show promise for reducing tricuspid regurgitation (TR) and improving quality of life.

The results follow similar data reported after the device was cleared for commercial use in Europe—CE Mark approval in Europe for the treatment of mitral regurgitation was announced in February 2019 and the TR approval came in October 2020.

According to Stephan Baldus, MD (Kardiologie Uniklinik Köln, Germany), where the Pascal device shines above other options—both available and in development—is in the “maneuverability [and] steerability of the device inside the valve and inside the right ventricle.” Baldus presented the TriCLASP data today at EuroPCR 2022. “In a way, [that abolishes the] risk of being entangled given that you can elongate the system and safely retract it.” The second unique feature is that it can independently grasp tricuspid valve leaflets to increase the likelihood of proper positioning.

For the TriCLASP study, Baldus and colleagues enrolled 74 patients (mean age 80 years; 58% female) with primarily functional (84.2%) but also degenerative (5.3%) and mixed/other (10.5%) TR. TR was severe or greater in 83% of the population and 96% had atrial fibrillation.

All but two patients had successful device implantation (97%), and procedural and clinical success were each 78%. The mean number of devices implanted per patient was 1.8, and patients stayed in the hospital for an average of 5.1 days.

Among the 67 patients in whom 30-day follow-up data were available, the total composite “massive adverse event rate” was 3.0%. One patient died 14 days after the procedure after having a stroke following a massive bleeding event, and another died of pneumonia after 40 days. Three patients were hospitalized for heart failure.

Core lab assessment showed marked improvement in TR severity, with more than 90% reporting no more than moderate TR after 30 days (P < 0.001); 88% achieved at least one TR grade reduction. Additionally, NYHA class improved, with 56% graded to be class I or II at 30 days compared with slightly more than 20% at baseline (P < 0.001). Kansas City Cardiomyopathy Questionnaire (KCCQ) score increased by about 13 points and 6-minute walk distance went up by about 38 meters (both P < 0.001).

Baldus said the study will be ongoing with follow-up through 5 years.

Commenting on the study findings, session co-moderator Corrado Tamburino, MD, PhD (University of Catania, Ferrarotto Hospital, Italy), said a similar scenario is taking place for TR as was seen for mitral regurgitation. “We implanted the clip for many years without any evidence from studies,” he said. “It was an unmet clinical need.”

Baldus agreed and said that even so, the randomized clinical trials ongoing for TR are still needed and will likely be “better” than they were in the mitral space since “we are [getting the data] at an earlier stage.”

Several Device Options

During the same session, Philipp Lurz, (Heart Center Leipzig, Germany), presented additional 30-day data from the TriClip bRIGHT study on the first 300 patients implanted with the TriClip and TriClip G4 edge-to-edge repair devices (Abbott). TCTMD previously covered 30-day data on the first 200 patients last year.

Implant success was 98% and acute procedural success was 91%; two clips were used per patient on average. At 30 days, 71% of patients reported moderate or lower TR (P < 0.0001). Among the 108 patients who received the newer TriClip G4 device, independent grasping was used in 69% of cases and 75% reported moderate or lower TR at 30 days (P < 0.0001).

Overall, three major adverse events (1.0%) were reported, including one CV death and one stroke. Four patients required tricuspid valve reintervention or reoperation (1.3%) and 20 reported major bleeding (6.7%). NYHA functional class improved, with 78% in class I or II at 3 days, and KCCQ score improved by 18 points (P < 0.0001 for both).

Lastly, Rebecca Hahn, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), presented 1-year data from the CLASP TR study, previously covered by TCTMD at the American College of Cardiology 2022 Scientific Session last month.

“We’re starting to build up a good body of evidence that’s really telling us that these procedures are very feasible, [and] there’s pretty good safety data as well, which I think is very important,” session co-moderator Edwin Ho, MD (Albert Einstein College of Medicine, Bronx, NY), told TCTMD. “It gives us the time and space to develop the even more robust clinical trials that we need from the clinical impact perspective, especially around prognosis. Those studies often take longer. So then to see the initial symptom benefit that we’re seeing in these studies is really important.”

With many up-and-coming devices in the TR space, it’s good to have options, Ho continued. “The whole idea about tailoring device selection is one of the hot topics in the field in general,” he said. “It will be something that we have to customize to anatomy so it’s exciting to see all of these options. In a lot of the sessions here, people have done slight predictions in how they think the field is going, and I think it’s hard to tell, but the more we learn and also the timing of when we’re treating patients, earlier versus later, we can wind up defining what we use more and more in the future.”

Right now, many patients with TR are presenting late in their disease progression, which makes them particularly difficult to treat. “As the evidence builds up in the future, I think that these patients will actually be recognized a little earlier, be treated potentially a little earlier, which helps avoid the extremes in anatomy,” Ho said. “That’s why I think the field is a little bit of a shifting space, that over time I think we’ll actually continue to evolve in a lot of ways.”

TriCLASP: Tricuspid Repair With Pascal Safe, Effective at 30 days | tctmd.com

 

MitraClip Helps for Atrial Functional MR: MITRA-TUNE

In patients with preserved LV function and/or AF, edge-to-edge repair leads to improved MR grade and symptom relief.

PARIS, France—Patients with atrial functional mitral regurgitation (MR) appear to benefit from edge-to-edge leaflet repair, data from the MITRA-TUNE registry suggest.

In patients with mitral regurgitation stemming from left atrial enlargement with atrial fibrillation (AF) but with preserved LV function and no leaflet degeneration, MitraClip (Abbott) repair led to significant improvement in their MR status and symptoms, as well as positive remodeling of the left atrium and mitral annulus.

Antonio Popolo Rubbio, MD (IRCCS Policlinico San Donato, Milan, Italy), who presented the results of MITRA-TUNE during a late-breaking clinical update at EuroPCR 2022, explained that atrial functional MR differs from classic functional MR in that it occurs in patients with AF and/or heart failure with preserved ejection fraction (HFpEF).

“It’s a newer subtype of secondary mitral regurgitation that has been introduced in the last 10 years,” Rubbio told TCTMD. In this case, he said, patients have normal systolic left ventricular function and normal leaflet motion. In AF, though, the left atrium can become stiff and fibrotic, which can cause severe dilatation of the left atrium. This results in dilation of the mitral annulus and impaired annular contractility.

Even in the absence of AF, however, HFpEF can result in atrial functional MR. “It’s like a vicious cycle in which we have preserved ejection fraction, left atrium dilatation with increased left atrium pressure that can cause the electrical disorders,” said Rubbio.

The prevalence of atrial functional MR is unknown, he added, although it’s thought to range between 3% and 15%. It is associated with a higher risk of adverse outcomes compared with AF patients without functional MR, but current guidelines do not provide any recommendations on how to best treat it, which is problematic in elderly patients.

“We have surgical treatment for younger people, or for those with fewer comorbidities,” said Rubbio. “In this case, we’re talking about an elderly cohort who weren’t eligible for surgery.” While mitral regurgitation can be influenced by medical therapy, these patients have HFpEF for which pharmacologic treatment is extremely limited, he said.  “It’s not so easy to give medical therapy. Most of these patients were treated with beta-blockers because of their arrhythmia but beta-blockers are not the main treatment in preserved ejection fraction.”

MITRA-TUNE Follow-up in a Small Cohort

For the MITRA-TUNE study, investigators retrospectively reviewed 1,135 symptomatic patients with more than moderate functional MR who underwent transcatheter mitral valve repair with MitraClip in seven Italian centers. The analysis focused solely on 87 patients (median age 81 years) with mostly persistent/permanent AF and functional MR without structural leaflet abnormalities and preserved left ventricular function. Prior to the procedure, two-thirds of patients had MR grade 4+ while 83% of patients had NYHA class III/IV symptoms.

At 30 days, the cumulative risk of all-cause mortality was 5.0%. After a median follow-up of 371 days, the vast majority of patients had an improvement in MR—47 of 53 patients with available echo data had an MR grade ≤ 2+. Similarly, for the 61 patients with data, 48 (79%) were now in NYHA class I/II after a median follow-up of 489 days. Echo analysis of the left atrium and mitral annulus also showed that use of the MitraClip was associated with significant positive remodeling. In a multivariable analysis, postprocedural MR grade ≥ 2+ and a mitral annular diameter > 35 mm were both independent predictors of all-cause mortality/HF hospitalization.

To TCTMD, Rubbio said the study has limitations, noting foremost that it is a retrospective analysis. In terms of future research, he said it will be important to understand how patients respond to MitraClip in addition to the restoration of normal sinus rhythm, such as after catheter ablation of AF. In addition, they will need to understand more about managing pharmacotherapy for these patients, not only with beta-blockers but also with oral anticoagulation.

Ulrich Schäfer, MD (Marienkrankenhaus Hamburg, Germany), one of the panelists during the late-breaking clinical trials session, said that atrial functional MR appears to be a good indication for edge-to-edge repair with MitraClip, noting that the phenotype is clearly an “annular disease problem” given that larger mitral annular diameters were independent predictors of worse outcomes.

Rubbio noted that while the outcomes suggest edge-to-edge repair could be an option for elderly patients unable to undergo surgery, the results could still be improved. With MitraClip, previous studies have shown that the most-favorable results are seen in patients with residual MR grade 1+. The introduction of newer-generation MitraClip devices should help operators achieve better outcomes, he said.

“We know that it’s an important difference,” said Rubbio. “Moderate residual mitral regurgitation is considered a negative predictor of outcomes when compared with mild mitral regurgitation. An acceptable result is not the same as an optimal result.”

MitraClip Helps for Atrial Functional MR: MITRA-TUNE | tctmd.com

 

Better Durability With Self-Expanding TAVI? Clues From UK TAVI

While the analysis considered patients treated with early devices, the findings have implications for lifetime planning, experts say.

PARIS, France—Updated data from the UK TAVI registry tracking long-term valve function hints that severe structural valve degeneration (SVD) affected nearly 6% of patients who received an early generation TAVI device. Also, severe deterioration appears to be more common with balloon-expandable than with self-expanding devices.

Noman Ali, BMBS, PhD (Leeds Teaching Hospitals NHS Trust, England), who presented the data here at EuroPCR 2022, acknowledged to TCTMD the pitfalls of the observational data and any comparisons drawn between devices.

“Obviously there are limitations given that they are first-generation valves, but the fundamental differences between the Sapien and the CoreValve haven’t changed in terms of one being supra-annular [and] one being intra-annular, one being balloon-expandable and one being self-expanding,” Ali told TCTMD. “Those differences are still present in the current iterations. There have been some improvements, but I think the fundamental message is that the supra-annular design appears to lend itself to a slower rate of degeneration, and I think that will still be seen in newer valves. The overall numbers might be lower in both, but I suspect that difference might still be present.”

A previous snapshot from UK TAVI, of just 149 patients followed for a median of 5.8 years, pointed to a slightly higher incidence of moderate SVD, with roughly half of the cases due to new aortic regurgitation and 43% to restenosis.

In this latest data with longer follow-up, however, investigators focused on severe SVD and zeroed in on differences between valve types among 221 adults who underwent TAVI at one of 11 centers in the United Kingdom between 2007 and 2011. All patients had undergone echocardiograms postprocedure and again at a time point beyond 5 years, allowing for assessment of SVD.

Valve Durability Insights

Investigators for UK TAVI used a definition of severe SVD adapted from the European task force committee guidelines. These specify at least one of the following: mean gradient of ≥ 40 mmHg and/or ≥ 20 mmHg increase from baseline; a peak velocity ≥ 4 m/s and/or ≥ 2 m/s increase from baseline; or severe new or worsening intraprosthetic aortic regurgitation.

Median follow-up presented here today was 7.0 years (ranging from 5 to 13 years), with 43 patients being more than 10 years post-TAVI. Just over two-thirds of patients (mean age 79) had been treated with the CoreValve (Medtronic), while 31.3% had received a Sapien/Sapien XT valve (Edwards Lifesciences). Transfemoral access was used in 79%, and valve deployment was successful in 97.2% of patients.

Over the extended follow-up period, 13 patients (5.9%) developed severe SVD a median of 7.8 years post-TAVI. In three cases, SVD was due to aortic regurgitation, and in 10 the underlying cause was stenosis. Hemodynamic function of the valve remained stable for most patients and in some cases actually improved with time. Analyzed by valve type, however, a higher proportion of patients treated with the balloon-expandable valve versus those treated with the self-expanding valve developed severe SVD (11.9% vs 3.5%, P = 0.02).

Speaking with TCTMD, Ali said he hopes these data can help inform lifetime management considerations for patients.

“We know that we’re going to be using TAVIs in younger and younger patients going forward, and this just adds another variable to the decision-making process,” he said. “You’ve got to consider the possibility of TAVI-in-TAVI, which perhaps favors a balloon-expandable valve to begin with, followed by a self-expanding valve. Then you’ve got to balance that with the prospect that that may degenerate faster.”

On the other hand, for a slightly older patient, you might consider a self-expanding valve to begin with, since its longevity may more closely match that of the patient.

“I think the take home is just integrating this information into the overall decision-making process for lifetime management of these patients, and I think we need to move, as heart teams, from just looking at what’s the best valve for this patient now to thinking about what’s going to be the next valve beyond this,” he said. “When TAVI first came out, we were looking basically out to 5 years because patients were 85 years old. Now when they’re 70 years old, we have to be thinking 15, 20 years down the line, and I think this data can be used as part of that decision-making process.”

We need to move, as heart teams, from just looking at what’s the best valve for this patient now to thinking about what’s going to be the next valve beyond this. Noman Ali

Commenting on the data for TCTMD, session moderator Jonathan Schwartz, MD (Sanger Heart & Vascular Institute, Charlotte, NC), noted that the UK TAVI numbers represent the largest data set for post-TAVR patients at or beyond 10 years.

“It’s hard to extrapolate too much from it as there were only 43 patients in that cohort, but as mentioned, it’s the best we have to date,” said Schwartz.

This analysis, he pointed out, focused exclusively on leaflet durability related to regurgitation and stenosis, but other factors likely also play a role in SVD, including endocarditis, paravalvular leak, commissural alignment, proper valve expansion, supra-annular versus intra-annular design, and associated postprocedure gradients.

Ongoing questions around hypoattenuated leaflet thrombosis and mobility, and how those may influence valve durability, remain unanswered, he said. In the UK TAVI patients, “how much of this is true leaflet deterioration? We know younger, active patients, and end-stage renal disease patients on hemodialysis show leaflet deterioration at a significantly accelerated rate than older, sedentary, nondialysis patients.”

Another consideration is leaflet material, Schwartz continued, noting that some devices use bovine pericardium and others porcine. “This has changed little from the earlier-generation valves,” he said, although polymer-derived leaflet platforms are an area of active investigation.

“Time will tell where valve innovation heads from here, with significant improvements made since the time of the bioprostheses used in this study. While current TAVR platforms have evolved greatly since the those presented in this trial, this is an enlightening first look into the long-term outcomes for TAVR patients, and newer valves likely will only show even better results,” said Schwartz.

Correction: This story has been corrected to address an error in an earlier headline, which misidentified balloon-expandable devices as having better durability in this analysis.

Better Durability With Self-Expanding TAVI? Clues From UK TAVI | tctmd.com

 

Intravascular Imaging Boosts Outcomes in Left Main PCI: ROLEX

Guidelines recommend IVUS to improve left main stenting. Based on these data, to not do so is “unacceptable,” one expert says.

PARIS, France—Patients with left main coronary artery disease fare relatively well when treated with a zotarolimus-eluting stent, but even better outcomes could be achieved if operators used intracoronary imaging.

Those are the main findings from the ROLEX registry, a multicenter, international, prospective study of patients with left main CAD undergoing PCI with the Resolute Onyx stent (Medtronic).

Lead investigator Giuseppe Tarantini, MD, PhD (University of Padua, Italy), who presented the results during the late-breaking clinical trial session at EuroPCR 2022, said the findings from the imaging subanalysis should be considered hypothesis-generating, but they do suggest intravascular imaging should be used more frequently given the demands and challenges of left main CAD revascularization.

“What is amazing is that when you went with IVUS, you upsized the stent size in more than 50% of the cases and we observed less than half the event rate than in the overall population,” Tarantini told TCTMD.

During a panel discussion following the presentation, Marie-Claude Morice, MD, PhD (Institut Cardiovasculaire Paris Sud/Cardiovascular European Research Center, France), said she, too, believes interventional cardiologists should be regularly using intracoronary imaging in left main CAD. The risk of cardiac mortality at 1 year in ROLEX was 2.7%, a rate she described as “not nothing.”

“I don’t think it’s correct anymore not to do imaging when you perform left main interventions,” said Morice. “For me, it’s unacceptable [that use of imaging] is not systematic.”

The same holds for Robert A. Byrne, MBBCh, PhD (Mater Private Hospital, Dublin, Ireland). “We’re among interventional cardiologists here, but it’s important to realize there is scrutiny in the left main space because the results of the surgeons are good,” he said. “We need to be sure that the bar is high in terms of the technical interventional result.”

That scrutiny Byrne hinted at stems recent clinical trials comparing PCI to CABG surgery, most notably EXCEL. As documented on TCTMD, there has been an ongoing debate over how to interpret the trial results that led the European Association for Cardio-Thoracic Surgery to pull their support for the left main recommendations of the European Society of Cardiology (ESC). In Europe, CABG is class I indication for patients with left main CAD regardless of SYNTAX score, while PCI is a class I indication for patients with low anatomical complexity (SYNTAX score 0-22) and a class IIa recommendation for those with intermediate anatomical complexity (SYNTAX score 22-32).

In patients with left main disease, the ESC guidelines state that IVUS should be considered to optimize stent implantation (class IIa).

ESC Says IVUS Should Be Considered

The ROLEX registry included patients with significant left main stenosis of low-to-intermediate anatomical complexity (SYNTAX score ≤ 32) treated with the zotarolimus-eluting stent. The majority of patients (64%) had a SYNTAX score suggesting intermediate anatomical complexity. One-third of patients had left main CAD plus an additional stenosis, while nearly 60% had left main disease with multivessel CAD.

At 1 year, the primary endpoint of target lesion failure was 5.1% in the 450 patients who underwent PCI. Rats of cardiac death, target-vessel MI, and ischemia-driven TLR were 2.7%, 2.7%, and 2.0%, respectively. The rate of stent thrombosis was 1.1%, but Tarantini pointed out that two patients discontinued dual antiplatelet therapy for unknown reasons. Periprocedural MI occurred in 3.8% of cases.

The risks of TLF were significantly lower among those treated with intracoronary imaging compared with those treated with angiography alone. Among the 200 patients in whom operators used either IVUS or OCT, the rate of TLF was 2.0%. In contrast, the TLF rate among 250 patients treated with angiography-guided PCI was 7.6%.

We’re among interventional cardiologists here, but it’s important to realize there is scrutiny in the left main space because the results of the surgeons are good. Robert A. Byrne

Tarantini noted that patients treated with intracoronary imaging were more likely to be implanted with the extra-large Resolute stent, which measures 4.5 to 5.0 mm and capable of expansion to 6.0 mm. With previous workhorse stents, expansion might be possible to 5.0 mm and a little beyond, but in doing so there is a risk of compromising the stent’s structural integrity, he said.

“As a matter of fact, 18% of patients in our registry needed to receive an extra-large platform,” said Tarantini. “This is important because the new sizes are a little bit different. They have wider struts, which means more radial strength, and wider cells. The stents were designed for very large vessels where you have larger branches. You need wider cells to have access to the collateral branches, all without losing radial strength.”

As an operator, Tarantini said that even though physicians might use these stents in a minority of cases—21.5% of patients in ROLEX received the 4.5-5.0 mm Resolute Onyx stent versus 14.2% treated with angiography alone—their use “matters,” said Tarantini.

Byrne, on the other hand, said it’s still an open as to whether there’s an unmet need for larger stents in selected patients with left main CAD. Newer-generation DES perform quite well in this space, he said, although he noted there are benchtop data suggesting better postexpansion capability with certain stents, such as Resolute Onyx and Synergy Megatron (Boston Scientific). Whether that means these stents perform any better than the latest-generation workhorse stents isn’t known, said Byrne.

Speaking to the overall results, Byrne said the rate of TLF at 1 year appears reasonable for patients with left main CAD but pointed to another study for a better understanding of PCI for left main disease.

“I would say that over the last 12 months, the best data that we have comes from the Sabatine et al meta-analysis, which included all four of the left main trials together,” said Byrne. “That suggests that in patients with left main stem disease undergoing revascularization there is little difference in mortality [between PCI and CABG].”

That meta-analysis, presented late in 2021, was facilitated by the ESC to review the evidence on left main revascularization and to help inform the next guidelines.

Intravascular Imaging Boosts Outcomes in Left Main PCI: ROLEX | tctmd.com

 

Robotic PCI Safe, Feasible in Noncomplex Cases: R-Evolution

Using the R-One device shaves procedural time and reduces operator radiation exposure, especially with experience.

PARIS, France—Robotic PCI is safe and feasible for patients and improves safety and ergonomics for the operator, according to the R-Evolution study.

A clinician using the R-One system (Robocath; Rouen, France), which received CE Mark approval in 2019, uses joysticks in the control station to remotely operate catheters, guidewires, balloons, and stents, theoretically without being exposed to harmful radiation. At this time, Eric Durand, MD, PhD (Normandie University, Rouen, France), explained to TCTMD, the system can only manipulate one wire at a time, with the potential to put a second on standby.

“It’s very easy to use,” he said, presenting the data today during EuroPCR 2022. “There are single-use cassettes that we have to change for each patient like the other system, [but it’s a] very easy platform. . . . I think we are at the beginning of the story.”

The data are not the first to explore the potential of robots in the cath lab, with prior studies of various systems showing technical success and improved operator wellness and even the ability to protect staff against COVID-19.

Pieter Smits MD, PhD (Maasstad Hospital, Rotterdam, the Netherlands), who was a co-investigator on the R-Evolution study and served as a co-moderator during the session, told TCTMD that he is “always the person who’s running into walls” when playing video games, but with this particular system, he has proved more adroit. “This joystick manipulation was really easy to learn actually.”

And as someone with a history of orthopedic injuries, Smits added that not having to wear heavy lead for the procedures was a welcome experience, as was the knowledge that he was exposed to less radiation. However, he admitted that robotic PCI “takes away a little bit [of] the fun.”

Panelist Chaim Lotan, MD (Hadassah-Hebrew University, Jerusalem, Israel), said he worries about not being able to rely on tactile feedback that interventionalists spend years honing. “Can we train the robot to feel the touch?” he asked, following the study presentation.

Pedro Lemos, MD, PhD (Hospital Israelita Albert Einstein, São Paulo, Brazil), who has used the Corindus CorPath system for 2 years and was also part of today’s panel discussion, said he’s been pleasantly surprised by the experience. “When we started doing the robotic PCI, we thought that we would lack or miss this type of feeling,” he said. “It’s totally untrue.”

Durand also pointed out that in some ways, using the system is like teaching fellows. “I have no hand feeling, only eye feeling. So, we are comfortable with that. It is not a problem for me.”

High Clinical, Technical Success

For the study, Durand and colleagues included 62 patients with 64 lesions (mean age 65.4 years; 80.6% male) treated across six European centers between 2019 and 2021. Patients were excluded if they had lesions longer than 38 mm or wider than 4 mm or if they had severe calcification and tortuosity, bifurcations, ostial lesions, restenosis, left main lesions, or saphenous vein grafts. Radial access was used primarily (96.8%), and postdilatation was mandatory in about one-third of cases.

Clinical success was 100%, with no MACE through 1 month, and technical success was 95.2%. There were three conversions to manual PCI, two of which were not related to the robot. Median procedure duration was 20 minutes shorter for fully robotic procedures compared with those that were not (17.5 vs 37.5 minutes). Additionally, median contrast volume was lower (84.5 vs 110 mL). Lastly, radiation exposure as measured under and on top of the lead apron was 84.5% and 77.1%, respectively, lower for an operator who remained in the robotic control station compared to someone right next to the patient.

Lastly, the operators observed improved results with increased experience, with less manual conversion (0 vs 10.7%; P = 0.09), lower total procedure duration (35.5 vs 45.2 minutes; P = 0.008), and shorter robotic procedure duration (17.5 vs 22.2 minutes; P = 0.07), thus indicating a learning curve.

Future Potential

Durand explained that, in reality, the radiation exposure to the operator would depend on who else might be working alongside them. “If you work alone, you have to move [near] patients to advance the guidewire, the stent, or balloon in the robot and you have to go back to your chair in your radioprotected station,” he said. “But if you’re working with a fellow or with a nurse who will introduce the wire, the balloon . . . you can stay [in] your chair and you can work very comfortably with very good ergonomic position to treat the patients.”

Lemos explained that robotic PCI has “changed the environment” of his cath lab, mostly for the better. However, he said, “if you think about the training of the new fellows, it’s challenging because . . . how [can they] learn how to do the manual things? We’ll see how it goes.”

For now, Durand recommended training new interventionalists in both manual and robotic PCI, if only because operators will need to be able to convert on a dime to manual PCI if using the robot.

Smits added that while the tactile feedback is gone with robotic PCI, “you have a device that will offer you very precise positioning. So, you miss something, and you add something.”

Durand said the biggest hurdles going forward are expense, especially since a new cassette has to be used with each new patient, as well as the effort needed to convince operators to get on board and gain experience. Next, he’d like to see “more registries showing that it is feasible in more-complex lesions,” Durand said, adding that while he’d want a randomized study comparing manual and robotic PCI, deciding what to show with a trial like that would be difficult given that lower radiation exposure has already been proven. “Noninferiority as compared to manual PCI?” he wondered. “Probably. It’s the only thing we need to convince everyone.”

With robotic systems like R-One, said panelist David Moliterno, MD (University of Kentucky, Lexington), there is the potential to perform remote interventions in the future. “I think it’s taking interventions to a broader arena,” he said. “Say, neurointerventions, right? There are plenty of interventional cardiologists, but very few interventional neurologists to do acute stroke thrombectomy. I could see if you were at home and your fellow could at least get access, you could easily do a stentriever and pull out the thrombus and really expand care to acute stroke patients.”

 

JenaValve Trilogy Meets the Challenge of AR in Early Real-World Use

Results with the TAVI device, the first approved for use in aortic regurgitation, now need to be replicated on a larger scale.

PARIS, France—New results from Europe provide reassurance that TAVI with the Trilogy heart valve system (JenaValve Technology) can be safe and effective patients with aortic regurgitation (AR), even outside of a trial setting.

Just a year ago, Trilogy received CE Mark approval for use not only in AR but also in aortic stenosis, making it the one device in the world approved for both indications. And, as TCTMD reported last fall, initial results were positive. It has yet to get Food and Drug Administration clearance for marketing in the United States, where the ALIGN-AR pivotal trial is currently recruiting participants.

Today, in a hotline session at EuroPCR 2022, Alexander R. Tamm, MD (Johannes Gutenberg-Universität, Mainz, Germany), presented data on 45 consecutive patients at high surgical risk treated at six German centers.

Speaking with the media, Tamm noted that until recently, TAVI in AR was done off-label using devices designed for aortic stenosis. This unique disease subset has posed “procedural challenges and poorer outcomes,” said Tamm.

Aortic valve calcification, which plays a key role in anchoring most TAVI devices, tends to be absent or mild in most cases. Trilogy, to meet this need, “features unique locators that [allow] the valve to ‘clip’ onto the native leaflets,” he explained. “Thus, it’s enabling anchoring in pure AR patients with noncalcified valves.”

Tamm told TCTMD that “the technique is the game changer.” With Trilogy, three locators clip to the aortic leaflets and then the stent frame clips to the locators with the valve in between, “so you will achieve 100% anchoring,” he said. This allows the device to be fixed and sealed in place once it opens, which protects against valve migration and paravalvular leak.

He described it as an “easy, manageable procedure,” with device times of 20 minutes at the start of the learning curve and 10 minutes with experience.

Commenting on the study for TCTMD, Raj Makkar, MD (Cedars-Sinai Medical Center, Los Angeles, CA), said, “These results are excellent, given that these are the first few implants of these operators in the real world. . . . If the numbers are replicated with a larger sample size, this is for sure, in my opinion, going to be a really important device in treating patients with aortic regurgitation.”

As for the device design, assets include the fact that it’s self-expanding, Makkar said. It also offers “dual anchoring” at the level of the leaflets plus, thanks to oversizing, at the annulus.  Moreover, “the hemodynamics are almost best in class,” he noted, adding that “the way this device is placed, there is commissural alignment, so I think access to coronary arteries is going to be good.”

Technical Success, Safety, Effectiveness

In their series, all patients presented with moderate-severe or severe AR. Mean age was 77 years, 40% of patients were female, and the mean EuroSCORE II was 7.1%. Seven in 10 patients were in NYHA class III or IV. Nearly one-third had previously undergone cardiac surgery. More than half (58%) had an LVEF ≤ 50%.

All cases were done via transfemoral access, with the majority (82%) performed under conscious sedation. Two involved postdilatation. Mean procedure time was 77 minutes.

Technical success with a mean gradient < 20 mm Hg and reduction of more than one AR grade, the primary efficacy endpoint, was achieved in 100% of patients. None developed stage 2/3 acute kidney injury. There were no instances of major or life-threatening bleeding, and the minor bleeding rate was 6.7%. One patient (2.2%) had a major vascular complication.

Regarding safety, none of the patients required conversion to open surgery, had a stroke, or died. Nine patients (23%) needed a new pacemaker.

At discharge, mean aortic valve gradient was 4.04 mm Hg and mean aortic valve area was 2.62 cm². Most patients had no or trace paravalvular regurgitation (56% and 36%, respectively), while 8.9% had mild.

Individuals “ineligible or at high risk for SAVR were previously without treatment options, and our results give confidence to TAVI as a lifesaving procedure for AR patients,” he said, adding that future studies are needed in “larger cohorts and expanded patient populations.”

Although the pacemaker rate might seem to be on the high side, prior studies show this is typical with native AR. A 2020 paper published in Mayo Clinic Proceedings, for example, showed rates of around 20% with TAVI and 12% with surgery, Tamm said. “It’s a different population [from aortic stenosis]. We have to learn about that, I think. Maybe they’re prone to conduction disturbances.”

Makkar drew attention to the pacemaker rate as well, and he predicted this may decrease over time. Moreover, “in a lot of these patients with AR, a pacemaker rate of 18% or 20% is not a bad bargain in terms of avoiding super-high-risk surgery,” he pointed out.

In aortic stenosis, Trilogy may prove useful for certain scenarios, such as when the coronaries are low, said Makkar. With this anatomy, “there is a higher risk of occlusion of the ostia, because the leaflets can be pushed out in front of the coronaries,” he explained.

JenaValve Trilogy Meets the Challenge of AR in Early Real-World Use | tctmd.com

 

Shorter DAPT Sufficient Even in Complex HBR Patients: MASTER DAPT

Complex HBR patients had the most to gain from longer DAPT, but even here, the shorter regimen seemed to hold up.

PARIS, France—One month of dual antiplatelet therapy (DAPT), compared with 3 months or longer, is sufficient for PCI patients at high bleeding risk (HBR) regardless of procedural complexity, according to a subanalysis of MASTER DAPT.

In the ongoing quest to define optimal DAPT duration following PCI, these data indicate that even complex patients at higher risk of bleeding may not require a longer course of treatment than their noncomplex counterparts, researchers say. The findings are in line with the original MASTER DAPT results, presented last year at the European Society of Cardiology meeting and published in the New England Journal of Medicine.

In fact, during a press briefing at EuroPCR 2022, Marco Valgimigli, MD, PhD (University of the Italian Switzerland, Lugano), told TCTMD it’s likely that past studies of longer-term DAPT, such as PEGASUS-TIMI 54, “clearly overtreated” these patients by putting them at “threefold higher bleeding risk and no signal of benefit.”

One-month DAPT in HBR patients is now “standard of care that I’m implementing more and more in my practice with the caveat of stent thrombosis and in-stent restenosis,” Valgimigli continued. For the latter groups, he bases his decision-making around dual drug duration on a patient’s individual bleeding risk.

But commenting on the study for TCTMD, David Kandzari, MD (Piedmont Heart Institute, Atlanta, GA), said in the United States, physicians are “very much compelled to prolong dual antiplatelet therapy for high-bleeding-risk patients with complex disease” with the thought that this will reduce events.

“Many practitioners are, rather than proactively stopping dual antiplatelet therapy and transitioning to single antiplatelet therapy, instead waiting for the bleeding event to occur and then going to single antiplatelet therapy,” he said. “Or alternatively—and maybe to be fair, more commonly—treating patients for longer durations of 6 months or 1 year, whereas [in the past] they might have prolonged it for 12 months or a lifetime for those particular patients instead.”

HBR Patients

For the subanalysis, presented today at EuroPCR 2022 by Pascal Vranckx, MD, MBA, PhD (University of Hasselt, Belgium), and simultaneously published in the European Heart Journal, the researchers used the Giustino criteria to define complex PCI, including at least one of the following:

• Three vessels treated
• Three or more stents implanted
• Three or more lesions treated
• Bifurcation with two stents implanted
• Total stent length > 60 mm
• Chronic total occlusion as the target lesion

The slightly more than one-quarter of the total study population considered to be complex had similar NACE (all-cause death, MI, stroke, and major bleeding), MACCE (all-cause death, MI, and stroke), and major or clinically relevant nonmajor bleeding outcomes at 1 year compared with the noncomplex patients.

One-Year Outcomes

The results remained consistent when the researchers used more-comprehensive definitions of complex PCI as well as in complex PCI and/or ACS and complex PCI and ACS populations, Vranckx reported.

Strategy Change

Discussing the findings, panelist Petr Widimský, MD, DrSc (Charles University, Prague, Czech Republic), said the study will enable him to wait until a month after PCI to decide on a DAPT strategy, as opposed to choosing an option immediately following the procedure, as he has been doing. “This could be a complete change of our strategy,” he said.

Similarly, panelist Eliano Navarese, MD, PhD (Nicolaus Copernicus University, Bydgoszcz, Poland), said “this study’s a practical exemplification of reality in a conundrum on the patients we see daily.” While the margin of noninferiority used here is “relatively large,” he added that he is confident in the findings because of the large sample size.

It will likely take more to convince US physicians. “What it would take to transition practice in the United States would be greater education among the noninterventional cardiovascular community,” Kandzari predicted. “The awareness of shorter-duration trials in the interventional space is increasing among the interventional cardiologists, and I still would say there’s a lot of opportunity for education there, but certainly that hasn’t translated beyond the interventionalists to the broader cardiovascular community, at least in clinical practice.”

Additionally, because interventional cardiologists tend to be involved more in follow-up care in Europe than in the United States, this could explain some of the discrepancy, Kandzari added.

As for the variability in how complex PCI, as well as high bleeding risk, can be differently defined in clinical practice, he said it might not be that big of a deal since doctors rely on “more of a gestalt or a perception” as opposed to hard and fast criteria when managing care. “Lesion complexity differs because of variability in interventionalists’ interpretation of the angiogram and their skill sets, too.”

“Are there always going to be one-off cases where people are going to think that this is really not a complex lesion or it is a complex lesion?” Kandzari asked. “To be sure that will occur, but I think that those types of lesion characteristics, there’s good consensus across the interventional community that those would qualify as such.”

Next, Kandzari would like to see more work looking at what the ideal agent is when transitioning to single antiplatelet therapy. “Aspirin therapy confers its own individual bleeding risks because of its irritative effects on the GI tract,” he explained. “Clopidogrel has a lower risk of bleeding. More-potent ADP antagonists or P2Y12 inhibitors prasugrel and ticagrelor might confer a higher bleeding risk.”

Lastly, because MASTER DAPT involved use of the bioresorbable Ultimaster stent (Terumo), which is not commercially available in the United States, both the researchers and Kandzari say the findings cannot be applied to patients who receive different stents.

“Many doctors would say this is a class effect, that it’s not related to the stent, that the trial results stand on their own with regard to the duration of dual antiplatelet therapy,” Kandzari said. “I still feel in many ways that each stent needs to be held to its own standards just based on early lessons with early-generation drug-eluting stents, that it’s not a class effect. . . . Whether it’s translational to other drug-eluting stents, I think, to be fair, has to be proven.”

CRUZ-HBR

Also during the session, David Leistner, MD (Charité – University Hospital Medicine, Berlin, Germany), presented results of the CRUZ-HBR study, which showed noninferiority of the sirolimus-eluting Supraflex Cruz stent (SMT; Surat, India) with regard to the composite endpoint of CV death, non-target-vessel MI, and clinically driven TLR compared with the biolimus DCS in 466 HBR patients at 1 year.

Interestingly, BARC type 3 to 5 bleeding was reported in 5.9% of HBR patients at 1 year—significantly more than the 0.7% in the non-HBR patients (P = 0.001)—even though only 23.8% of them were still on DAPT at 12 months (52.3% of the non-HBR patients remained on DAPT).

At this point, panelist Hany Eteiba, MD (Nuffield Health, Glasgow, Scotland), said, it would not be worth revisiting the DAPT guidelines for HBR patients yet. “For high-risk bleeding, it is very challenging in that it will increase proportionately because of that increasing aging population and comorbid conditions, etc,” he said. “Therefore, it is difficult to extrapolate when you randomize a specific stent with biodegradable polymer versus no nonbiodegradable polymer, this is no polymer whatsoever. And then you’ve got prasugrel and you’ve got aspirin, you’ve got clopidogrel. I think it’s difficult to extrapolate.”

For co-moderator Chaim Lotan, MD (Hadassah-Hebrew University, Jerusalem, Israel), “the take-home message is the importance of late bleeding. We as cardiologists are very worried for the subacute thrombosis, which is less than 1% in most cases, but once we see 6% of major, major bleeding, I think it underestimates the importance of the 1% subacute thrombosis. We have to be more worried about the late bleeding complications than about the early results. And I think that all of us should be rethinking how to manage the long-term treatment in those patients.”

Shorter DAPT Sufficient Even in Complex HBR Patients: MASTER DAPT | tctmd.com

 

Registry Data Hint at MACE Benefit With Renal Denervation

PARIS, France—Patients who spend the most time with optimally controlled blood pressure after renal denervation have a lower rate of major cardiovascular events than do those with less-than-ideal blood pressure, a new study suggests.

At 3 years, the MACE rate for those who spent more than 50% of time in therapeutic range (TTR) was 2.9% compared with 10.3% for patients who failed to achieve any TTR and 6.2% for those who spent less than 50% of the time with optimally controlled blood pressure (P < 0.0001).

The new data, from the Global SYMPLICITY Registry of more than 3,000 patients with hypertension who underwent radiofrequency ablation with the Symplicity Spyral catheter (Medtronic), are likely the best the field will see when it comes to clinical outcomes, according to researchers.

Felix Mahfoud, MD (Universitätsklinikum des Saarlandes, Homburg/Saar, Germany), who presented the results today at EuroPCR, said blood pressure-lowering has always been the accepted standard for antihypertensive therapy and it shouldn’t be any different for renal denervation.

“If you want to run an outcomes study, you’d need 20,000 patients enrolled and it would never happen,” said Mahfoud. “These data are encouraging. It has limitations because we’re lacking a control group here, but it shows for the first time that patients with a higher time in therapeutic range have reduced events. That should convince people that lowering blood pressure with renal denervation also translates into improved outcomes.”

David E. Kandzari, MD (Piedmont Heart Institute, Atlanta, GA), coprincipal investigator of the SYMPLICITY clinical trials program, appeared to agree, noting that TTR can be a useful metric to assess the clinical impact of renal denervation. While the registry data do have drawbacks, they are the first hinting that lowering BP with renal denervation lowers the risk of MACE. Moreover, they appear to suggest that it doesn’t matter whether it’s lifestyle, medication, or radiofrequency ablation that shifts blood pressure downwards.

“It’s not so much how you get there, but that you get there,” said Kandzari.

World Hypertension Day

Sofie Brouwers, MD, PhD (Cardiovascular Center Aalst/OLV Hospital Aalst, Belgium), who wasn’t involved in any of the studies, said the initial enthusiasm with renal denervation—those exuberant, halcyon days when investigators reported massive reductions in systolic blood pressure—led some to suspect that medication for hypertension might one day be obsolete.

“I think that was really exaggerated, of course, but I think the data now are really promising on safety and efficacy,” Brouwers told TCTMD. She emphasized that the cornerstone of treatment for hypertension will always remain lifestyle modification, which means increasing physical activity and losing weight if overweight or obese. “Lifestyle should always be the basis of care, with pharmacological therapy optimized, but I do think renal denervation is useful. We use it very often in the hypertension clinic for specific patients who come to us.”

Brouwers said the ideal patient for renal denervation is one with uncontrolled hypertension. That might mean a patient who refuses to take any medication, but also those who are taking multiple medications who can’t get their BP under wraps. “I think there’s a wide variety of data showing where it can be used,” said Brouwers.

Last September, the European Society of Hypertension published a new position statement recommending that renal denervation be considered the third option for the treatment of hypertension alongside lifestyle modification and drug therapy.

At EuroPCR, clinicians devoted a full session to the interventional treatment of hypertension, using the opportunity to highlight two renal denervation programs with different technologies: SYMPLICITY with radiofrequency catheter ablation and RADIANCE with ultrasound-based technology (Paradise; ReCor Medical). The presentations were held to coincide with World Hypertension Day, which is intended to raise awareness about monitoring and treating high blood pressure in the approximately 1 billion people living with hypertension worldwide.

Despite advances in care, a significant proportion of patients with high blood pressure remain undiagnosed or are insufficiently treated with antihypertensive medications, said Mahfoud. The burden of hypertension is increasing rapidly in lower- and middle-income countries but is also increasing in high-income countries. Two large meta-analyses—one published in 2016 and the other in 2021—showed that even modest reductions in systolic blood pressure reduced the risk of major CVD events, including stroke, heart failure, ischemic heart disease, and cardiovascular death.

The problem isn’t that hypertension is not taken seriously, said Mahfoud. Pharmaceutical advances prove that point. “We have available drugs, but patients don’t like them or don’t take then.” Data has shown that nearly one in five patients with resistant hypertension aren’t taking any medication at all and nearly half are only partially adherent to treatment, he said.

Global Symplicity Registry and SPYRAL

The Global SYMPLICITY Registry analysis included 3,077 patients enrolled to date, nearly half of whom had a history of heart disease. Six months after renal denervation, office systolic blood pressure was reduced 13.2 mm Hg. By 3 years, that reduction was 16.7 mm Hg. In terms of 24-hour ambulatory blood pressure, patients undergoing renal denervation had a 9.0-mm Hg reduction by 3 years.

Focusing on TTR, which is a metric that has emerged as a measure of control of chronic disease conditions, the time in range increased from 30.6% at 6 months to 34.9% at 3 years. Measured another way, patients spent an average of 55 days in TTR at 6 months and 377 days in TTR at 3 years.

Investigators observed significantly lower risks of MACE and cardiovascular death among patients with higher TTR. For those with more than 50% in range, cardiovascular mortality was 1.5% compared with 4.0% for those who spent no time in range and 3.5% for those who a TTR below 50%. The stroke rate was 5.4%, 2.4%, and 0.1% for those who spent no time, partial time, and more than 50% in range.

On multivariate analysis, each 10% increase in TTR during the first 6 months of treatment was associated with a 16% lower risk of MACE

In a similar analysis, the SPYRAL HTN-ON MED investigators presented data from that trial showing that renal denervation also led to better BP control. When TTR was defined as office systolic BP ≤ 140 mm Hg, 28.0% of patients randomized to renal denervation were optimally controlled compared with just 13.0% of those treated with the sham procedure. When ambulatory BP ≤ 140 mm Hg was the TTR criteria, 47.8% of those treated with renal denervation were in range compared with 32.0% of those treated with sham.

Kandzari, who led the SPYRAL HTN-ON MED analysis, said TTR is a good metric to use in hypertension as physicians increasingly recognize the lifetime burden of disease. In past studies, TTR has been shown to be an independent measure of BP control, as well as an independent predictor of cardiovascular events.

Pooling Two RADIANCE Studies

Finally, in the third presentation, investigators presented data based on a pooled analysis of RADIANCE-HTN TRIO and SOLO, two sham-controlled trials of ultrasound-based renal denervation. The two studies included different patient populations standardized on a single medical regimen. The RADIANCE-HTN SOLO study included patients with mild-to-moderate hypertension while RADIANCE-HTN TRIO examined the treatment effect of ultrasound-based renal denervation in patients with resistant hypertension.

Despite taking 2.5 medications, on average, at screening, blood pressure was significantly elevated in the RADIANCE patients regardless of how it was measured.

“In other words, these are the types of patients we want to reach on World Hypertension Day,” said lead investigator Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY). “Patients who, despite seeing their physicians, have blood pressures that are quite elevated. We know given their age that if they continue with this blood pressure over time, they are going to have adverse sequalae.”

In the combined analysis, the mean between-group reduction in daytime ambulatory systolic blood pressure at 6 months was 4.8 mm Hg. With mean home systolic blood pressure, the between-group difference was 5.4 mm Hg favoring renal denervation (P < 0.001).

While renal denervation doesn’t cure hypertension, the data suggest it can be used safely and effectively as an adjunct to medical therapy across a range of hypertension severity, said Kirtane. At 6 months, patients treated with renal denervation required fewer antihypertensive medications and were less likely to need an additional antihypertensive agent during the 6-month follow-up, he said.

Michel Azizi, MD, PhD (Paris Descartes University, France), who presented the RADIANCE analysis at EuroPCR 2022 emphasized that while the between-group difference is just 5 mm Hg, it is clinically significant. Such a reduction in ambulatory BP, he said, would reduce major CVD events by roughly 10%, as well as reduce the risk of stroke and heart failure by 13% and 14%, respectively.

“This is a large difference,” Azizi told TCTMD. “Also, these are average values. We have large variability from one subject to another, and we have people with a 20-mm Hg reduction in blood pressure, but we are still struggling to find those who are really, truly responsive [to treatment].”

Also, while the between-group difference was 5 mm Hg, renal denervation did result in a 14-mm Hg reduction in mean ambulatory BP. The placebo effect, in other words, was quite large in these trials, said Azizi.

Clinical Work

To TCTMD, Brouwers said that while antihypertensive medications are cheap and widely available and have been proven to lower the risk of MACE, there are some patients who simply refuse to take drugs no matter how strongly she recommends treatment. In this era of patient-centered care, patient preference is important, she said, noting that you can’t force people to take medication.

But there are other things to be tried prior to an invasive procedure, she suggested.

In clinic, one tactic she uses is to emphasize not only the potential risks of stroke and ischemic heart disease, but also the risks of dementia or sexual dysfunction associated with hypertension, which is something that can get patients’ attention. If patients do take medication, her aim is to get patients to goal as quickly possible—within 3 months at least—to show that treatment works, increasing the patient’s confidence in the treatment and hopefully boosting adherence.

Registry Data Hint at MACE Benefit With Renal Denervation | tctmd.com

 

Changes in Cardiac Damage After AVR Tied to 2-Year Outcomes

PARIS, France—Patients with more-severe cardiac damage prior to undergoing aortic valve replacement are more apt to die in the 2 years after their procedure, data from the PARTNER trials show. What’s more, changes in the extent of that extravalvular damage at 1 year also impact 2-year mortality risk, investigators say.

The findings, with Philippe Généreux, MD (Morristown Medical Center, NJ), as lead author, were published today in the Journal of the American College of Cardiology to coincide with their presentation at EuroPCR 2022.

In 2017, Généreux and colleagues published an anatomy-based classification system for cardiac damage prior to AVR, linking baseline damage to outcomes. This time around, the researchers “characterized the evolution and the progression and regression of cardiac damage after aortic valve replacement,” Généreux told TCTMD.

Aortic valve disease doesn’t exist in isolation, he explained. “Even if you fix the valve and improve [its function], you still have to work on extravalvular cardiac damage. It’s not infrequent that you see patients that have great results after the TAVR or surgical AVR but still come back to the hospital with heart failure, A-fib, RV dysfunction, etc, etc.”

Aortic valve replacement, when it’s done late, is not reversing the damage.Maral Ouzounian

The message from this analysis is that “maybe we need to intervene earlier before cardiac damage is present,” he said, emphasizing that waiting too long can have consequences. Another takeaway is that this presents an opportunity to optimize therapy “upstream before the AVR and also downstream after the AVR,” Généreux advised.

Maral Ouzounian, MD, PhD (Toronto General Hospital, Canada), who didn’t take part in the research, said the paper is important and likely to be impactful.

What these data show is that “very few patients are coming without extravalvular damage. . . . This is quite late in the game,” Ouzounian told TCTMD. Also striking is the finding that “aortic valve replacement, when it’s done late, is not reversing the damage,” she noted. “A lot of them got worse or stayed the same, and I think that goes against what is common thinking about aortic valve disease—that by the time patients become symptomatic, you do AVR and their cardiac function and outcomes will improve.”

Patients should be referred earlier for treatment, Ouzounian stressed, and “we should really not be only focusing on the aortic valve and its effect on the left ventricle, but also [consider] the downstream effects on global cardiac function.”

Benoy Shah, MBBS, MD (Southampton General Hospital, England), speaking with TCTMD, touched on similar themes. “If you look at what’s happening with the whole of the heart and not just the aortic valve, you can get some quite interesting insights,” he observed.

The assertion that aortic valve disease needs to be detected earlier is a valid one, said Shah, but “I think we need to be careful about jumping to the conclusion that this means automatically we need to be intervening earlier” on the valve.

He pointed out that the classification system captures aspects apart from aortic stenosis. “There are so many other things that can affect those parameters,” he stressed, so it’s important to think beyond the AVR itself. “It’s absolutely crucial that in these patients that already have a pressure load on the heart from aortic stenosis, that we really manage their other risk factors as well.”

Perhaps eventually there will be a comprehensive framework that captures both the severity of aortic stenosis and the extent of cardiac damage, Shah suggested. “Can they, or should they, in some way be amalgamated?”

Philippe Pibarot, DVM, PhD (Laval University, Quebec, Canada), who presented the abstract today at EuroPCR, told attendees that there is room for refinement. Based on evidence from asymptomatic patients—here the cohort was exclusively symptomatic—the ideal timing for AVR seems to be between stage 1 and 2. But it’s clear, however, that “there are different types of stage 2, so I think we need to further refine this staging classification, maybe with blood biomarkers such as troponin and BNP,” he said, adding that cardiac magnetic resonance might also prove helpful in identifying responders versus nonresponders to AVR.

Just 15% Saw Improvement

For their study, the researchers pooled 1,974 patients who underwent AVR in the PARTNER 2 and 3 trials and who had complete transthoracic echocardiography (TTE) data for staging at baseline. Risk was inoperable/extreme for 17.3% of the cohort, intermediate for 54.3%, and low for 28.4%. Sixty percent were treated with TAVI and 40% with SAVR.

Patients’ extent of cardiac damage prior to their procedure varied:

• Stage 0: no damage (6.1%)
• Stage 1: LV damage (14.5%)
• Stage 2: left atrial or mitral valve damage (51.4%)
• Stage 3: pulmonary vasculature or tricuspid valve damage (20.9%)
• Stage 4: RV damage (7.1%)

Baseline damage was associated with mortality 2 years after AVR (HR 1.51 per higher stage; 95% CI 1.32-1.72), as well as the combined risk of mortality and heart failure (HF) hospitalization. Even after adjusting for baseline cardiac damage, the extent of cardiac damage at 1 year predicted both endpoints.

Risk at 2 Years by Baseline Cardiac Severity

	Stage 0	Stage 1	Stage 2	Stage 3	Stage 4
All-Cause Mortality	2.5%	7.1%	14.6%	28.2%	28.2%
Mortality/HF Hospitalization	4.1%	13.4%	22.9%	38.7%	39.0%

At 1 year, 1,120 patients were alive and had paired TTE assessment from baseline and follow-up.

Cardiac damage remained unchanged for 60% of patients and worsened in 25% over the year since AVR. Just 15% saw an improvement. Of the patients in stage 1, for example, 40.9% progressed to higher stage and 7.2% died by 1 year. Of the patients who started out in stage 2, 24.7% saw worsening cardiac damage and 15.2% died.

These shifts in stage also were linked to 2-year mortality, such that patients whose damage improved saw a decrease in risk (adjusted HR 0.49) and those whose damage worsened saw an increase in risk (adjusted HR 1.95). Similar patterns were seen for the death/HF hospitalization composite.

Independent predictors of stage deterioration included hypertension (OR 1.73; 95% CI 1.01-2.96) and SAVR as the index procedure (OR 2.04; 95% CI 1.52-2.74).

Généreux said this is an argument for better blood pressure control. “Yes, you remove the aortic stenosis but you still have an increased afterload with hypertension,” he commented.

The link between progression and SAVR “is not surprising, since it is a more-invasive procedure,” he observed. Additionally, the paper notes, “SAVR is known to be associated with an increased rate of new-onset atrial fibrillation after AVR, increased risk of patient-prosthesis mismatch with reduced LV mass regression, and postoperative RV dysfunction related to cardiopulmonary bypass process or suboptimal RV protection during surgery.”

The Right Treatment at the Right Time

Ouzounian said it’s necessary to “dig into exactly why some patients improve and others don’t.” The analysis supports being “more aggressive at treating concomitant cardiac issues that may lead to poor prognosis, like mitral insufficiency or tricuspid insufficiency,” she commented.

Watchful waiting . . . only works if you’re actually watchful.Benoy Shah

This staging system should now be studied prospectively, added Ouzounian. Perhaps “we will learn that intervening in the asymptomatic stage, or even in the moderate stage, may be the best way to prevent the irreversible damage from happening.”

That information is in the works. EARLY TAVR finished enrollment 6 months ago, said Généreux, while PROGRESS recently began enrolling patients. Both trials are tracking cardiac damage.

Shah, regarding the current analysis, highlighted the cohort’s older age (mean 81 years) and comorbidity burden: nearly one-third had diabetes, 92% had hypertension, 55% had CAD, and half were in class III heart failure. It’s unclear how the staging system would translate in younger patients. Another question for younger patients is how earlier intervention might result in the need for repeat procedures, he added.

On the whole, prompt treatment for those who need it is clearly important, Shah said. Yet there are many challenges in terms of timing. “Watchful waiting” in patients who haven’t yet undergone AVR “only works if you’re actually watchful, if you’re doing it very regularly almost like a hawk. You’ve got to keep a really close eye on these patients. Absolute maximum follow-up should be 6 months. Sometimes you might need to see them every 3 or 4 months. And of course a lot of health systems don’t have the capacity to see people that frequently,” he said, adding that even after the decision is made to intervene, there can be further months-long delays before the procedure is done.

 

Changes in Cardiac Damage After AVR Tied to 2-Year Outcomes | tctmd.com

 

Potassium Ferrate Patch Speeds Hemostasis, Discharge After Radial PCI

PARIS, France—Use of a potassium ferrate hemostatic patch instead of conventional dressings following radial PCI can lead to “substantial” benefits that go beyond trimming the time to hemostasis and discharge plus compression, results from the single-center ARCH trial show.

As lead medical investigator, Claudio Proscia, MD (Liverpool Heart and Chest Hospital, England), explained during a EuroPCR 2022 late-breaking trial presentation today, the hemostatic patch, known as the StatSeal (Biolife), includes a hydrophilic polymer that dehydrates blood and absorbs exudate, while the potassium ferrate agglomerates solids and proteins. Earlier studies, including the recent STAT2 trial, have shown that the hemostatic dressing, in combination with compression, leads to earlier compression removal and fewer vascular complications.

Senior ARCH investigator, Rod Stables, DM, BM BCh (Liverpool Heart and Chest Hospital), told TCTMD that while he’d expected to see a benefit with the patch over standard dressings plus compression, he was “shocked” by the magnitude of the difference, saying that the results have the potential to be practice-changing for his hospital and others.

Lounge Access

The trial was conducted in the “business-class lounge-style” day care facility of Liverpool Heart and Chest Hospital, which is the ward dedicated to same-day discharge patients. As such, said Stables, ARCH would be applicable to other centers that also have swift-discharge protocols following elective or stabilized PCI procedures.

“We wanted to improve the patient’s experience,” Stables explained. “That was the number one aim,” he said. “We wished to reduce the period of hemostasis, which for some patients can be extremely uncomfortable—the pressure is annoying, they have limited mobility, they are always under observation, and can’t be discharged.”

Moreover, he continued, delays to hemostasis and the need for monitoring consume nursing care. Having nurses and clinicians “tied down” with hours of observation ultimately means they have less time for other patients, less time for catching other problems that might arise, and less time for discussing things like rehabilitation and risk factor management.

For lead nursing investigator, Rhian Brown, RN (Liverpool Heart and Chest Hospital), the trial succeeded in what she perceives as its chief aim—namely, “the fact that patients could go home to their own families, to their homes and beds, quicker than before.” Some would have already been in the hospital for several nights, having been transferred from another facility, she noted to TCTMD.  “It’s always nice to go home to your own place.”

ARCH Objectives

ARCH set out to randomize 3,000 patients (a mix of elective and stabilized ACS patients transferred from other hospitals) to a conventional dressing with 2-hour compression (the control), to conventional dressing and 1-hour compression, or to the StatSeal hemostatic dressing followed by 1 hour of compression. The TR Band (Terumo) was used for compression in all patients, and dressings were left in place for up to 3 days. The trial was stopped early on the recommendation of the data and safety monitoring board when the hemostatic dressing emerged as the clear front-runner.

Among the 2,114 patients recruited and randomized, just 5.2% of the 708 randomized to the hemostatic patch failed to reach hemostasis within the allotted time period, as compared with 50% of those receiving conventional dressing plus 2 hours of compression (703 patients), and 62% of those with conventional dressing/1-hour compression (703 patients), a statistically significant difference for all comparisons.

Time from randomization postprocedure to complete hemostasis also favored the patch at a median of 72 minutes, as compared with 136 minutes and 166 minutes for the conventional dressings used for 1 and 2 hours, respectively. Adverse outcomes and rates of radial artery occlusion were not significantly different between groups, but rates of discharge delays related to radial care were significantly higher in the conventional-dressing groups.

According to Stables, the trial results still need to be replicated and validated at other centers, but he expects a forthcoming cost-efficacy analysis at Liverpool to show a benefit to the hemostatic dressing, and that it would do so at other places with similar protocols for early discharge.

“We are prepared to discharge a patient 4 hours after PCI, but if you are not and you [aim to discharge] at 8 or 12 hours, then the economic gain won’t be as great. But the proportion of patients who aren’t ready to go home is more with conventional dressings, the number who stay overnight is more, and the number who have to stay extra hours is more: for us there will be a big financial gain, but whether that translates to other hospitals remains to be seen.”

The cost of the dressing in the UK, Stables noted, is “about 20£.”

They investigators plan to work on a cost-modelling analysis that would allow centers to apply the results to their own hospital protocols in order to better understand the cost impact of switching to the hemostatic patch, Proscia noted at the close of his talk.

To TCTMD, he also highlighted the novelty of the “lean, efficient, pragmatic” trial design, with research documentation integrated completely into the electronic medical records, allowing for seamless randomization of patients, who consented before the procedure, before sheath removal at the end.

Although the trial was planned prior to the COVID-19 pandemic and subsequent downturn in PCI procedures, it was able to efficiently enroll a diverse and nonselected group of patients, Proscia added.

During the Q&A, panelists made the point that patch devices like these are likely only needed for PCI patients who have heparin on board and are likely not needed for radial angiography. But Stables, following the session, clarified that heparin 70 units/kg with ACT guidance was used in all cases in ARCH, something he characterized as a “key factor in minimizing subsequent radial artery occlusion.”

In response to a separate question, Proscia acknowledged that a patient satisfaction survey had not been a part of the trial design.

Commenting on the study results for TCTMD, Jordan Safirstein, MD (Morristown Medical Center, NJ), lead author for STAT2, observed that the results of ARCH are “very similar,” with very low rates of radial artery occlusion and low rates of complications in general.

The PCI cohort was larger in ARCH, he noted, because it ultimately included some inpatients, which STAT2 did not. ARCH also showed a considerably faster time to hemostasis.

Commenting on the study results for TCTMD, Jordan Safirstein, MD (Morristown Medical Center, NJ), lead author for STAT2, observed that the results of ARCH are “very similar,” with very low rates of radial artery occlusion and low rates of complications in general.

The PCI cohort was larger in ARCH, he noted, because it ultimately included some inpatients, which STAT2 did not. ARCH also showed a considerably faster time to hemostasis.

Potassium Ferrate Patch Speeds Hemostasis, Discharge After Radial PCI | tctmd.com

 

Summary sheets by EuroPCR:

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