Consistently attracting over 11,000 delegates, EuroPCR remains one of the largest interventional meetings on the planet and this year’s packed programme did not disappoint, reports Dr Christopher Allen from this year’s meeting in Paris, France.
Coronary intervention – Trials
As the first ever blinded, sham-controlled, percutaneous coronary intervention (PCI) trial, demonstrating a non-statistically significant increase in exercise time at six weeks from PCI over optimal medical therapy (OMT), to say the publication of ORBITA (Percutaneous Coronary Intervention in Stable Angina) last year caused a stir would be quite the understatement. Regardless of your interpretation of the data,1 or ensuing hyperbole,2 unanswered questions certainly remained.
Presentation of the previously blinded, invasive physiology data in the opening late-breaking clinical trials session here was therefore eagerly awaited. Published simultaneously in Circulation,3 the analysis highlighted a strong relationship between baseline fractional flow reserve (FFR)/instantaneous wave free ration (iFR) and reduction in inducible ischaemia on subsequent dobutamine stress echocardiography in the PCI cohort, underscoring the mechanistic basis of PCI and confirming those with the most ischaemic lesions have the most to gain. These intuitive observations were not replicated in angina relief, however, with no demonstrable relationship between baseline FFR/iFR and symptomatic improvement. While caution must be exercised in interpreting sub-analyses from an overall neutral trial, the findings nevertheless illustrate that symptom relief in stable angina is more complex than simply alleviating epicardial coronary stenoses. With plans for ORBITA-2 from the Imperial College team already in motion, there is certainly more to come on this story.
Later in the same session, the five-year results of FAME 2 (Fractional Flow Reserve-Guided Percutaneous Coronary Intervention Plus Optimal Medical Treatment Versus Optimal Medical Treatment Alone in Patients With Stable Coronary Artery Disease) highlighted another potentially ground-breaking observation, describing for the first time that in patients with ≥1 ischaemic coronary lesions (FFR < 0.8), PCI may be associated with reduced myocardial infarction over OMT.4 This signal, driven by spontaneous, rather than periprocedural myocardial infarction (MI), reached statistical significance when synthesised into a patient-level meta-analysis with two trials in which physiology was assessed in non-culprit lesions of ACS patients (DANAMI-PRIMULTI, Compare-Acute). Whether the latter two trials represent truly ‘stable’ patients was of course a subject of debate, but the observation that reducing ischaemia may influence ‘hard’ outcomes is certainly of interest. Further insight is expected from the large-scale (n≥5,000) ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), set to complete enrolment by the end of the year.
Away from the trial presentations, the live case transmissions were once again a big draw. None more so than a complex distal left main PCI case from Clinique Pasteur, Toulouse, France. Utilising an exciting new technique, coronary intravascular lithotripsy, operators Jean Fajadet and Bruno Farah prepared a seemingly undilatable, heavily calcified coronary lesion through the emission of pulsatile sonic pressure in a balloon-based technology adapted from that historically used to treat kidney stones. The achievement of an excellent procedural result sparked debate among delegates as to the technology’s potential role in PCI for calcified lesions, an ever-increasing problem in the face of an ageing population. Dr Jonathan Hill (King’s College Hospital, London) who was involved in the first-in-man study DISRUPT CAD (Shockwave Coronary Lithoplasty® Study),5 which described an excellent safety profile, commented: “It is a much more accessible and easier to use device than rotational atherectomy. If you know how to use a balloon, you can use it. While there will still be cases where atherectomy will be required, lithotripsy opens up calcium modification to a much broader group of interventionalists”. Having received its CE mark last year, the post-market study of the device (DISRUPT CAD II) has begun enrolment.
Valvular intervention – TAVI
Underlining the remarkable pace of progress in the transcatheter aortic valve implantation (TAVI) field, the original data presented this year centred on the remaining frontiers for the technology to tackle. A sub-group analysis of low risk (STS score < 3%) patients (n=254) included in the randomised SURTAVI (Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients) trial, demonstrated superior outcomes with a self-expanding transcatheter valve over conventional surgical aortic valve replacement (SAVR), with respect to the composite end point of all-cause death or disabling stroke (TAVI 1.5%, SAVR 6.5%, p=0.04).6 The results for TAVI in the challenging anatomical setting of patients with bicuspid aortic valves were also encouraging. Presenting a propensity matched analysis from the Transcatheter Valve Therapy (TVT) registry (1,792 bicuspid vs. 1,792 tricuspid patients,) Dr Raj Makkar (Cedars-Sinai Medical Center, Los Angeles, USA) described similar procedural technical success (97%), new pacemaker implantation rates (8–9%), 30-day, and 12-month mortality (2% and 10%, respectively).7 However, in a study that tracked longer procedural time, the 30-day stroke rate (2.5% vs. 0.9%) was higher in bicuspid patients.
In this regard, it is relevant that while magnetic resonance imaging points toward a reduced new ischaemic lesion volume with cerebral embolic protection devices, the reduction in clinical stroke rate (hazard ratio 0.55, 95% confidence interval 0.31-0.98, p=0.04, number-needed-to-treat = 33), coupled with the high cost, does not presently justify their routine use according to Dr Luca Testa, (Policlinico San Donata, Milan, Italy), on presentation of these meta-analysis data.8 Elsewhere, an analysis of six year follow-up from the NOTION (Nordic Aortic Valve Intervention) trial, importantly highlighted markedly lower rates of structural valve degeneration with a self-expanding TAVI valve over conventional SAVR bioprostheses in lower risk patients (4% vs. 23%).9
Valvular intervention – mitral
The late-breaking mitral trials highlighted increasing experience with a number of promising devices (repair and replacement) across a range of indications (e.g. degenerative and functional regurgitation, mitral annular calcification). Rounding off a packed session, Professor Simon Redwood (St Thomas’s Hospital, London) presented the 12-month results from MAVERIC (Mitral Valve Repair Clinical Trial) of the ARTO (MVRx) transcatheter annular reduction system for functional mitral regurgitation. Delivered transvenously, the system shortens the minor axis of the valve via an elegant adjustable bridge anchored between the coronary sinus and intra-atrial septum. Procedural results were promising, with reductions in mitral regurgitation (MR) severity mirroring a 15–20% mean decrease in anteroposterior annular diameter, left ventricular and left atrial volumes. These results were maintained out to one year, where 92% of patients (n=45) had MR ≤2+ and 80% New York Heart Association class I or II.10
Renal denervation – the phoenix rises?
The neutral results of the hotly anticipated SIMPLICITY-HTN (Renal Denervation for Resistant Hypertension) study in 2014 led to an enforced spell in the wilderness for renal denervation for blood pressure lowering. In addition to technical issues with lesion success, other critical issues that were identified included the commonplace nature of non-compliance, frequent inaccuracy in blood pressure measurement (more use of ambulatory blood pressure monitoring [ABPM] required), and appropriate patient selection, with severe refractory hypertension perhaps proving impossible to reverse.
The cautiously optimistic results of two new sham-controls in Paris are therefore of interest. In SPYRAL-ON, from the SIMPLICTY investigators, use of newly designed multi-electrode radiofrequency catheter (enabling circumferential lesions) successfully lowered blood pressure in patients with mild-moderate hypertension versus sham procedure.11 The benefits on ABPM continued out to six months, although the overall effect was modest (mean systolic BP -9mmHg, diastolic BP -6 mmHg). The sham-controlled RADIANCE-HTN SOLO tested an ultrasound energy device in patients with moderate hypertension off all medication, producing an effect of similar magnitude (mean systolic BP -8.5 mmHg, 24% vs. 3% 24-hour mean BP < 130/80 mmHg).12 Unresolved issues, particularly regarding the lack of a current metric to assess immediate procedural success, remain and the size of both studies was relatively small (n=80 and n=140, respectively). With larger studies already underway alongside trials of other technologies (e.g. carotid body stimulation, ROX coupler), the next few years promise to be informative.
NIHR BRC Clinical Training Fellow St Thomas’s Hospital, King’s College London
1. Al-Lamee R, Thompson D, Dehbi H-M et al., ORBITA investigators. Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial. Lancet 2018;391:31–40. https://doi.org/10.1016/S0140-6376(17)32714-9
2. Brown DL, Redberg RF. Last nail in the coffin for PCI in stable angina? Lancet 2018;391:3–4. https://doi.org/10.1016/S0140-6736(17)32757-5
3. Al-Lamee R, Howard JP, Shun-Shin MJ et al. Fractional flow reserve and instantaneous wave-free ratio as predictors of the placebo-controlled response to percutaneous coronary intervention in stable single-vessel coronary artery disease: physiology-stratified analysis of ORBITA. Circulation 2018; published online May 22nd 2018. https://doi.org/CIRCULATIONAHA.118.033801
4. Xaplanteris P, Fournier S, Pijls NHJ et al., FAME 2 Investigators. Five-year outcomes with PCI guided by fractional flow reserve. N Engl J Med 2018;379: 250-9. https://doi.org/NEJMoa1803538
5. Ali ZA, Brinton TJ, Hill JM, Maehara A et al. Optical coherence tomography characterization of coronary lithoplasty for treatment of calcified lesions: first description. JACC Cardiovasc Imaging 2017;10:897–906. https://doi.org/10.1016/j.jcmg.2017.06.021
6. Serruys P. SURTAVI: one-year outcomes of patients with severe aortic stenosis and an STS-PROM of less than three percent. Presented at EuroPCR 2018, Paris, France, 22nd-25th May 2018.
7. Makkar R. SAPIEN 3 outcomes for bicuspid vs tricuspid aortic valve stenosis: propensity matched results. Presented at EuroPCR 2018, Paris, France, 22nd-25th May 2018.
8. Testa L. Cerebral protection during TAVR reduces the incidence of major cerebrovascular events: results from an up-to-date systematic review and meta-analysis. J Am Heart Assoc 2018; May 4;7(10).pii: e008463. https://doi.org/10.1161/JAHA.117.008463
9. Sondergaard L. NOTION: longevity of transcatheter and surgical bioprosthetic aortic valves in patients with severe aortic stenosis and lower surgical risk. Presented at EuroPCR 2018, Paris, France, 22nd-25th May 2018.
10. Redwood S. MAVERIC: first presentation of the 1-year follow-up of the mitral valve repair clinical trial. Presented at EuroPCR 2018, Paris, France, 22nd-25th May 2018.
11. Mahoud F. Procedural details from the SPYRAL HTN OFF-MED trial of renal denervation for uncontrolled hypertension. Presented at EuroPCR 2018, Paris, France, 22nd-25th May 2018
12. Mauri L. RADIANCE-HTN SOLO: primary outcomes of a randomised sham-controlled, off-medication study in hypertension utilising an endovascular ultrasound renal denervation system. Presented at EuroPCR 2018, Paris, France, 22nd-25th May 2018.