The results of clinical trials presented at major international cardiology meetings in 2022 were reviewed. In addition to this, a literature search of PubMed, Medline, Cochrane library and Embase was completed, including the terms “acute coronary syndrome”, “atrial fibrillation”, “coronary prevention”, “electrophysiology”, “heart failure” and “interventional cardiology”. Trials were selected based on their relevance to the cardiology community and the potential to change future clinical guidelines or guide further phase 3 research. This article is based on previously completed work and does not involve any new studies of human or animal subjects performed by any of the authors.

Advances in Percutaneous Coronary Intervention

Several practice changing trials in Percutaneous Coronary Intervention (PCI) have been published this year (Table 1). Historically, PCI has been used to treat ischaemic cardiomyopathy, despite limited supporting evidence [1]. In the REVascularisation for Ischaemic VEntricular Dysfunction (REVIVED-BCIS2) trial [2], 700 patients with left ventricular ejection fraction (LVEF) ≤ 35% and extensive coronary artery disease (CAD), as defined by the British Cardiovascular Intervention Society (BCIS) jeopardy score, were randomised to PCI or optimal medical therapy (OMT). Over a median follow-up time of 3.4 years, PCI versus OMT alone did not result reduction in the primary composite outcome of death or hospitalization for heart failure [37.2% vs. 38.0%; HR 0.99; 95% confidence interval (CI), 0.78–1.27; P = 0.96] [2].

Table 1 Summary of key trials in percutaneous coronary intervention published in 2022

The optimal treatment for left main (LM) and multivessel CAD remains hotly debated. New observational data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) [3] compared outcomes among 10,254 such patients undergoing PCI (52.6%) versus coronary artery bypass grafting (CABG) (47.4%). PCI was associated with a 59% increased risk of death versus CABG after 7 years of follow-up (P = 0.011). Despite the limitations of observational data, findings are in keeping with the NOBLE study [4], supporting use of CABG where clinically appropriate in LM patients with additional multivessel CAD.

In contrast, a meta-analysis of 2913 patients from four RCTs (SYNTAXES, PRECOMBAT, LE MANS, and MASS II) undergoing PCI versus CABG for LM or multivessel CAD [5] did not report any significant difference in 10-year survival (RR 1.05; 95% CI 0.86–1.28), nor significant difference in the subgroup with LM disease alone or multivessel disease alone. This may reflect a lower extent of non-LM disease complexity in the four trials.

Of note, a new analysis from the SYNergy Between PCI With TAXUS and Cardiac Surgery Extended Study (SYNTAXES) evaluated mortality according to presence or absence of bifurcation lesions [6]. In the PCI group, those undergoing stenting of ≥ 1 bifurcation lesions versus no bifurcation stenting, had a higher risk of death at 10 years (30.1% vs. 19.8%; P < 0.001). Furthermore, a 2 versus 1 stent bifurcation strategy was associated with a higher risk of death at 10 years (HR 1.51; 95% CI 1.06–2.14). Conversely, in the CABG, the presence or absence of bifurcation lesions had no impact on mortality. As this was a post hoc analysis, results can only be considered hypothesis-generating, but are in keeping with previous data highlighting the complexity of bifurcations and the preference for a simple rather than a complex strategy where possible.

Female sex has been associated with worse outcomes following PCI related to smaller vessel disease. However, previous LM have been unclear and, given that LM has a larger diameter, more equivalent results. A substudy of the NOBLE trial [7] showed no difference in outcomes for male versus female, with both showing an excess of major adverse cardiovascular and cerebrovascular events (MACCE) with PCI at 5 years, although no difference in all-cause mortality.

For those undergoing PCI for LM disease, the IDEAL-LM (Individualizing Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in patients with left main stem disease) study [8] reported that a strategy of short 4-month DAPT (dual-antiplatelet therapy) plus a biodegradable polymer platinum-chromium everolimus-eluting stent was non-inferior to a strategy of conventional 12-month DAPT plus durable polymer cobalt-chromium everolimus-eluting stent (DP-CoCr-EES), with respect to a composite of death, MI or target vessel revascularisation at 2 years. However, the shorter DAPT strategy did not show any reduction in bleeding events.

The Complete Revascularization with Multivessel PCI for Myocardial Infarction (COMPLETE) trial previously reported that complete versus culprit-only PCI had lower risk of cardiovascular (CV) death/myocardial infarction (MI) over 3 years of follow-up. In a new pre-specified analysis [9], complete versus culprit-only PCI was associated with a greater absence of residual angina (87.5% vs. 84.3%; P = 0.013) and improved quality of life, as assessed via the 19-item Seattle Angina Questionnaire, including reduced physical limitation.

Improving PCI outcomes in patients with diabetes remains a focus of several trials. The Second-generation drUg-elutinG Stents in diAbetes: a Randomized Trial (SUGAR trial), which randomised 1175 patients with diabetes and CAD to an amphilimus-eluting stent (Cre8 EVO) vs. conventional Resolute Onyx stent, previously reported that the Cre8 stent met non-inferiority and was associated with a possible 35% reduction in Target Lesion Failure (TLF) at 12 months [10]. However, by 2 years [11], the difference in TLF was no longer significant (10.4% vs. 12.1%; HR 0.84; 95% CI 0.60–1.19) with numerical but non-significant differences in the individual components of cardiac death (3.1% vs. 3.4%), target vessel MI (6.6% vs. 7.6%), and target lesion revascularization (4.3% vs. 4.6%). While these 2-year results were disappointing, we await results of further studies of new stents in this clinical setting, including the ABILITY trial (NCT04236609) comparing an Abluminus DES + sirolimus-eluting stent system versus Xience.

Quantitative flow ratio (QFR), an angiography-based approach to estimate the fractional flow reserve, previously reported superiority versus conventional angiography guidance at 1 year in the FAVOR III (Comparison of Quantitative Flow Ratio Guided and Angiography-Guided Percutaneous InterVention in Patients With cORonary Artery Disease) trial [1]. New data report that the benefit with the QFR-guided strategy was sustained at 2 years, associated with a 34% reduction in the composite of death, MI or ischaemia-driven revascularization [8.5% vs. 12.5%; HR 0.66 (95% CI 0.54–0.81)] [12]. The degree of outcome improvement was greatest amongst those patients in whom the pre-planned PCI strategy was modified by QFR.

Current ESC guidelines give post-PCI surveillance with stress testing with a Class IIb recommendation. The POST-PCI (Routine Functional Testing or Standard Care in High-Risk Patients after PCI) trial randomised 1706 patients at 1 year after PCI to routine functional testing (nuclear stress testing, exercise electrocardiography, or stress echocardiography) versus standard care [13]. Use of routine functional testing failed to show any reduction in the primary outcome of death MI, or hospitalization for unstable angina at 2 years (5.5% vs. 6.0%; HR, 0.90; 95% CI 0.61–1.35; P = 0.62), supporting standard care in these patients.

Procedural time in graft-angiography studies may be much longer than a non-graft cases. The Randomised Controlled Trial to Assess Whether Computed Tomography Cardiac Angiography Can Improve Invasive Coronary Angiography in Bypass Surgery Patients (BYPASS CTCA), randomised 688 prior CABG patients to CTCA prior to coronary angiography versus standard care. Those who underwent prior CTCA had a shorter procedure duration (mean 17.4 vs. 39.5 min; OR − 22.12; 95% CI − 24.68 to − 19.56), less contrast during the invasive angiogram (mean 77.4 vs. 173 mls), less contrast-induced nephropathy (3.2% vs. 27.9%; P < 0.0001) and 40% greater patient satisfaction [14]. BYPASS CTCA thus supports consideration of prior CTCA particularly with more complex or uncertain graft location or patients at greater renal risk.

The 2018 ESC guidelines recommend radial access for PCI unless overriding procedural considerations. A new patient-level meta-analysis of 7 trials, incorporating 21,700 patients reported that, at 30 days, transradial versus transfemoral access was associated with a 23% reduction in all-cause mortality (1.6% vs. 2.1%; P = 0.012) and 45% reduction in major bleeding (1.5% vs. 2.7%; P < 0.001) [15]. However, transradial access is not without complications, the commonest of which is radial artery occlusion. In the RIVARAD (Prevention of Radial Artery Occlusion With Rivaroxaban After Transradial Coronary Procedures) trial, 538 patients were randomised following coronary angiography to rivaroxaban 10 mg once daily for 7 days versus standard care (no rivaroxaban) [16]. At 30 days, use of rivaroxaban was associated with a 50% reduction in radial artery occlusion as defined by ultrasound (6.9% vs. 13.0%; OR 0.50; 95% CI 0.27–0.91). Bleeding Academic Research Consortium (BARC)-defined bleeding events were numerically but not significantly higher in the rivaroxaban group (2.7% vs. 1.9%; OR 1.4; 95% CI 0.4–4.5). To assess whether distal radial artery puncture might reduce occlusion rates, the Distal Versus Conventional Radial Access DISCO-RADIAL) trial randomised 1,307 patients to distal versus conventional radial access [17]. Distal access was associated with shorter median hemostasis time (153 vs. 180; P < 0.001), but radial artery spasm was more common (5.4% vs. 2.7%; P = 0.015), crossover rates were higher (7.4% vs. 3.5%; P = 0.002) and no difference in the primary endpoint of occlusion on vascular ultrasound was noted at discharge (0.31% vs. 0.91%; P = 0.29).

While radial access now considered preferable, transfemoral access is still required in certain cases. As transfemoral operator skills may potentially decline through reduction in volume or lack of experience, ultrasound-guided access techniques are increasingly being used. The UNIVERSAL (Routine Ultrasound Guidance for Vascular Access for Cardiac Procedures) trial randomised 621 patients to femoral access with ultrasound guidance and fluoroscopy versus fluoroscopy alone [18]. Interestingly, and in contrast with previous trials, ultrasound guidance was not associated with significant reduction in the composite of BARC 2, 3, and 5 bleeding or major vascular complication at 30 days (12.9% vs. 16.1%; p = 0.25).

The strategy of multi-arterial CABG is endorsed by surgical guidelines but takes longer, is more technically demanding and can be associated with increased complications, such as deep sternal wound infections. An observational single-centre study by Momin et al. of 2979 patients undergoing isolated CABG (from 1999 to 2020) [19] reported those receiving total arterial revascularization had the longest mean survival (18.7 years) versus single internal mammary artery (SIMA) plus vein grafts 16.1 years; P < 0.00001) versus vein grafts only (10.4 years; P < 0.00001). Interestingly, survival with total arterial revascularization was not significantly different to SIMA plus radial artery ± vein grafting (18.60 years). This study supports the durability of arterial grafting, although conclusions are limited by its non-randomised design. Conversely, Saadat et al. stratified 241,548 patients from the Society of Thoracic Surgeons (STS) database undergoing isolated CABG in 2017 [20] into 3 groups: single arterial (86%), bilateral internal thoracic artery-multi-arterial (BITA-MABG; 5.6%), and radial artery multiarterial (RA-MABG; 8.5%). After risk adjustment, the observed to expected event (O/E) ratios showed no significant difference in mortality between the three strategies (1.00 vs. 0.98 vs. 0.96) and the risk of deep sternal wound infection was highest in the BITA-MABG group (1.91 vs. 0.90 vs. 0.96). Given the ongoing data uncertainty, results from the prospective randomised ROMA trial are eagerly awaited (NCT03217006).

Structural: Aortic Valve Interventions

There has been a dramatic expansion in transcatheter aortic valve interventions over the past decade [1]. A recent analysis of US registry data conducted by Sharma et al. reported a near doubling in transcatheter aortic valve replacement (TAVR) volume overall between 2015 and 2021 (44.9% vs. 2021, 88%, P < 0.01), including a 2.7 fold increase in those < 65 years (now similar to surgical aortic valve replacement (SAVR) (47.5% TAVR vs. 52.5% SAVR, P = ns) particularly in younger patients with heart failure (HF) (OR 3.84; 95% CI 3.56–4.13; P < 0.0001), or prior CABG (OR, 3.49; 95% CI, 2.98–4.08; P < 0.001) [21]. These numbers may further increase across all risk categories with the early long-term data from the seminal PARTNER (Placement of AoRTic TraNscathetER Valve Trial) trials awaited.

Emerging evidence from trials such as AVATAR (Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis) and RECOVERY (Early Surgery Versus Conventional Treatment in Very Severe Aortic Stenosis) suggests that early intervention for severe aortic stenosis (AS), before patients develop symptoms, may be of benefit [1]. In a pooled analysis of key trials (PARTNER2A, 2B &3) involving 1974 patients (mean age 81 years; 45% women), Généreux et al. evaluated the relationship between cardiac damage at baseline and prognosis in patients with severe symptomatic AS who underwent AVR (40% SAVR, 60% TAVI) [22]. Baseline cardiac damage was defined using a 0–4 scoring system (0 = no damage and 4 = biventricular failure). Baseline damage correlating strongly with 2-year mortality (HR 1.51 per higher stage; 95% CI 1.32–1.72) with each increase in stage conferred a 24% increase in mortality (P = 0.001) (from stage 0 = 2.5% to stage 4 = 28.2%) suggesting a role for earlier intervention. Several ongoing trials, such as EARLY TAVR (Evaluation of TAVR Compared to Surveillance for Patients With Asymptomatic Severe Aortic Stenosis), TAVR UNLOAD (Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure) and PROGRESS (Management of Moderate Aortic Stenosis by Clinical Surveillance or TAVR), aim to answer these questions directly.

Valve in valve (VIV) TAVR is being increasing utilised in patients with failed AVR; however, it remains unclear whether these patients do better with or without balloon valve fracture (BVF). In a registry analysis of 2975 patients undergoing VIV-TAVR (with balloon-expandable SAPIEN 3 or SAPIEN 3 Ultra) between December 2020 and March 2022, Garcia et al. [23] reported that BVF versus no BVF led to larger mean valve area (1.6 vs. 1.4 cm2; P < 0.01) and lower mean valve gradient (18.2 vs. 22.0 mm Hg; P < 0.01) but also to higher rates of death or life-threatening bleeding (OR 2.55; 95% CI 1.44–4.50) and vascular complications (OR 2.06; 95% CI 0.95–4.44). However, sub-analysis suggested the increase in mortality was mainly if BVF undertaken before VIV-TAVR (OR 2.90; 95% CI 1.21–6.94), whereas no difference was noted if undertaken after VIV-TAVR. This suggests that VIV-BVF should only be performed once the operator has a new TAVR in place.

While designed primarily for AS, conventional TAVR devices have sometimes utilised for the treatment of severe aortic regurgitation (AR). The novel trilogy heart valve system, specifically developed for AR, and was evaluated in 45 patients (mean age 77, 40% female, mean Euroscore 7.1%) with moderate to severe AR by Tamm et al. [24]. The primary endpoint, a reduction in ≥ 1 AR grade, was met in 100% of cases. There were no episodes of stroke, death, or conversion to open surgery, but 9 patients (23%) required permanent pacing.

Subclinical leaflet thrombosis (SLT) is a relatively common complication of TAVR; however, the optimal treatment strategies, whether with anticoagulation or antiplatelets, remain contested. The multicentre ADAPT TAVR (Edoxaban vs. DAPT in reducing subclinical leaflet thrombosis and Cerebral Thromboembolism After TAVR) randomised 229 patients (mean age 80.1 years; 41.9% men) undergoing TAVR for symptomatic severe AS, and without other indication for OAC, to edoxaban 60 mg or 30 mg once daily versus DAPT with aspirin and clopidogrel [25]. At 6 months, Edoxaban, by intention to treat analysis, was associated with a trend to reduced SLT as assessed by cardiac CT (9.8% vs. 18.4%; P = 0.076) and, in contrast to prior trials with DOAC post-TAVR, there was no difference in bleeding rates (11.7% vs. 12.7%; P = ns). Interestingly, a secondary per-protocol analysis focusing on patients with high compliance did reach statistical significance (19.1% vs. 9.1%; risk ratio 0.48; 95% CI 0.23–0.99). However, despite the use of serial brain MRI, there was no difference in the presence/number of cerebral lesions and no difference in neurocognitive outcomes including stroke at 6 months.

Giustino et al. reported a new secondary analysis from the GALILEO trial (Rivaroxaban-based Antithrombotic Strategy to an Antiplatelet-based Strategy After TAVR to Optimize Clinical Outcomes) which, as described previously [[4]], had randomised 1644 patients post-TAVR without an indication for oral anticoagulation (OAC) to rivaroxaban 10 mg plus aspirin versus DAPT with aspirin plus clopidogrel for 90 days, but was stopped early due to higher thromboembolic bleeding and mortality events in the Rivaroxaban group [26]. In the new analysis, thromboembolic events appeared to be associated with higher risk of mortality (HR 8.41; 95% CI 5.10–13.87) versus BARC 3 bleeding (HR 4.34; 95% CI 2.31–8.15). Furthermore, this mortality risk appeared higher than that conferred by known risk factors such as age (adjusted HR 1.04; 95% CI 1.01–1.08) and chronic obstructive pulmonary disease (COPD) (adjusted HR 2.11; 95% CI 1.30–3.41).

These findings along with previous data from ALANTIS (AntiThrombotic Strategy After Trans-Aortic Valve Implantation for Aortic Stenosis) and ENVISAGE-TAVI AF (Edoxaban Compared to Standard Care After Heart Valve Replacement Using a Catheter in Patients With Atrial Fibrillation) show how the role of DOACs post-TAVI remains uncertain [1]. However, given the devastating impact of thromboembolic events in this patient group, ongoing research is warranted. The absence of a bleeding signal with DOAC in ADAPT TAVR, in which most received lower dose Edoxaban, suggests that lower dose DOAC for a short duration while the valve is endothelialising may improve the risk/benefit ratio.

Another area of current contention is the use of cerebral embolic protection (CEP) to reduce risk of stroke. While current guidance does not mandate use, some operators use in high-risk cases [27]. Kaur et al. conducted a meta-analysis of 1,016 patients (mean age 81.3 years) from several randomised trials (DEFLECT III, MISTRAL-C, CLEAN-TAVI, SENTINEL, and REFLECT I and II) evaluating the TriGuard (Keystone Heart) and Sentinel devices versus standard care. At 30 days, CEP was not associated with a reduction in the primary outcome of all-cause stroke (RR 0.93; 95% CI 0.57–1.53), nor a reduction in mortality. Subsequently, the PROTECTED TAVR (Stroke PROTECTion With SEntinel During Transcatheter Aortic Valve Replacement) trial randomised 300 patients (mean age 72 years, 40% female) to CEP with a Sentinel device versus standard care [28]. Again, no significant difference in primary outcome of stroke at 72 h was noted (2.4% vs. 2.9%, P = 0.30), although numbers were relatively small. The results of BHF PROTECT TAVI (British Heart Foundation Randomised Clinical Trial of Cerebral Embolic Protection in Transcatheter Aortic Valve Implantation) plans to enrol 7000 patients and findings are eagerly awaited.

Stuctural: Mitral and Tricuspid Valve interventions

The favourable findings in COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [MR) helped lead to device approval [1]. However, it has been suggested the reason COAPT was favourable was the strict eligibility criteria, mandating LVEF ≥ 20% to ≤ 50%, left ventricular end-systolic dimension (LVESD) ≤ 70 mm and failure of aggressive medical therapy [4].

EXPAND (A Contemporary, Prospective Study Evaluating Real-world Experience of Performance and Safety for the Next Generation of MitraClip Devices) [29] was a prospective multicentre registry of 1,041 patients with site-reported MR 3 + /4 + were enrolled and received the MitraClip. A recent analysis compared 125 “COAPT-like” patients meeting COAPT inclusion criteria versus 128 “non-COAPT” patients. At 1 year, COAPT-like patients did not show any difference in the primary outcome of all-cause mortality (22.6% vs. 19.6%, P = 0.37) or heart failure hospitalisation (32.6% vs. 25%, P = 0.08). In keeping with their lower baseline MR severity, more non-COAPT patients achieved reduction in MR to mild or less (≤ 1 +) (97.2% vs. 86.5%), suggesting that Mitraclip may benefit patients beyond the strict COAPT criteria, but prospective randomised data are needed, such as the ongoing EVOLVE-MR (MitraClip for the Treatment of Moderate Functional Mitral Regurgitation).

Previous data from CLASP (Edwards PASCAL TrAnScatheter Mitral Valve RePair System Study) and CLASPII have validated the safety and efficacy of the Edwards PASCAL™ transcatheter valve repair system [1]. CLASP IID randomised 180 patients with severe degenerative symptomatic MR not eligible for surgery (mean age 81 years, 67% male, median STS 5.9%) to transcatheter Edge-to-Edge Repair (TEER) with the Pascal device (Edwards Lifesciences) vs. MitraClip (Abbott) device [30]. At 30 days, the Pascal device met criteria for non-inferiority with respect to the composite endpoint of CV death, stroke, MI, renal replacement therapy, severe bleeding and re-intervention (3.4% vs. 4.8%; P for noninferiority < 0.05). Of interest, the proportion of patients with MR ≤ 1 + was durable in the PASCAL group (87.2% discharge vs. 83.7% at 6 months; P = 0.317); whereas MitraClip outcomes showed some loss of efficacy (88.5% discharge vs. 71.2% at 6 months; P = 0.003). Although only interim data, this hints that the Pascal device may have superior durability.

ViV-transcatheter mitral valve replacement (ViV-TMRV) may be utilised in very high-risk patients without a surgical option on a case-by-case basis despite paucity of real-world outcome data. Bresica et al. retrospectively compared outcomes of 48 patients with bioprosthetic mitral valve (MV) failure undergoing ViV-TMRV (mean age 65 years, 63% female, mean STS 7.9%) versus 36 patients undergoing re-do MV surgery (mean age 58, 72% female, mean STS 7.1%) [31]. ViV-TMVR was not associated with improvement in 1-year survival (90% vs. 80%, P = 0.33) and was associated with higher average postprocedural gradient (8.9 vs. 5.7 mm Hg; P < 0.001). Thus, ViV-TMRV is a good option for high-risk patients, but in less comorbid patients may not provide as good a long-term benefit as surgery, particularly in those with smaller original surgical valves. Data to come from the ongoing PARTNER 3 (Mitral Valve-in-Valve trial) will be useful to help guide decision-making in such patients.

Several seminal trials, such as TRILUMMINATE (Abbott Transcatheter lip Repair System in Patients With Moderate or Greater TR), Triband (TranscatheterRepair of Tricuspid Regurgitation With Edwards Cardioband TR System Post-Market Study) and TRISCEND (Investigation of Safety and Clinical Efficacy After Replacement of Tricuspid Valve With Transcatheter Device), have led to a much greater focus on transcatheter tricuspid interventions [1].

CLASP TR (Edwards PASCAL Transcatheter Valve Repair System Pivotal Clinical Trial), a prospective single-arm multicentre study, evaluated 1-year outcomes of the PASCAL transcatheter valve repair system in 65 patients (mean age 77 ± 9 years, 55% female, mean STS 7.7%) with severe tricuspid regurgitation (TR) [32]. In keeping with the high baseline comorbidity, major adverse event rate was 16.9% (n = 11) with all-cause mortality 10.8% (n = 7) and 18.5% (n = 12) re-admitted with heart failure. Paired analysis demonstrated significant improvements in New-York Heart Association (NYHA) grade (P < 0.001), KCCQ score (P < 0.001) and 6-min walk test (6MWT) (P = 0.014). Importantly, the reduction in TR severity noted at 30 days (P < 0.001) was maintained at 1 year (100% had ≥ 1 grade reduction and 75% had ≥ 2 grade reduction, P < 0.001).

TRICLASP (Transcatheter Repair of Tricuspid Regurgitation With Edwards PASCAL Transcatheter Valve Repair System), a prospective, single-arm multicentre trial, evaluated 30-day outcomes in 67 of 74 patients (mean age 80 years, 58% female, mean STS 9%) undergoing the Pascal Ace transcatheter repair system for severe symptomatic inoperable TR [33] (Fig. 1). The primary composite outcome of major adverse events was 3% with 88% achieving ≤ 1 grade reduction in TR vs. baseline; P < 0.001), along with significant improvements in NYHA, KCCQ score, and 6MWT (P < 0.001). Longer term follow-up data are awaited.

Fig. 1

The PASCAL ACE™ system, designed for percutaneous tricuspid valve leaflet repair in severe tricuspid regurgitation. Reproduced with kind permission by Edwards Lifesciences LLC, Irvine, CA, USA

TriClip-Bright (An Observational Real-world Study Evaluating Severe Tricuspid Regurgitation Patients Treated With the Abbott TriClip™ Device) study [34], a multicentre, prospective study reported 30-day outcomes for 300 patients (78 ± 7.6 years) undergoing the Triclip Transcatheter valve repair system (Fig. 2). The primary endpoint of procedural success (survival to discharge) was met in 91%. Significant reductions in both NYHA and KCCQ score were noted at (P < 0.001). The trial is still actively recruiting, with a planned follow-up duration of 1 year.

Fig. 2

© 2022. All rights reserved

The TriClip™ G4 Transcatheter Edge-to-Edge Repair System (Abbott), designed for percutaneous tricuspid valve leaflet repair in severe tricuspid regurgitation. Reproduced with the kind permission of permission of Abbott,

Structural: Catheter Based Left Atrial Appendage and Patent Foramen Ovale Closure

While definitive studies to guide patent foramen ovale (PFO) closure practice are still lacking, a multidisciplinary consensus statement by SCAI was published this year [35] recommending closure in patients aged 18–60 with a PFO-associated stroke, platypnoea-orthodeoxia syndrome with no other cause, and systemic embolism with no other cause. Of note in the absence of PFO-associated stroke, the guidance does not recommend PFO closure in transient ischaemic attack, AF with ischaemic stroke, migraine, decompression illness or thrombophilia.

Several left atrial appendage closure (LAAC) devices have been approved in recent years with favourable long-term data published last year [1] for the Watchman LAAC device (Boston Scientific). The AMULET IDE trial (Amplatzer Amulet Left Atrial Appendage Occluder Versus Watchman Device for Stroke Prophylaxis) [36] trial randomised patients with non-valvular atrial fibrillation (AF), not suitable as anticoagulation to LAAC with an Amulet device (n = 934) versus Watchman device (n = 944). At 3 years, there was no difference in the primary composite endpoint of CV mortality, ischaemic stroke or systemic embolism (11.1% vs. 12.7%, P = 0.31) all-cause mortality (14.6% vs. 17.9%; P = 0.07) or major bleeding (16.1% vs. 14.7%; P = 0.46). Similarly, updated data from the US LAAC registry, comparing the Watchman FLX to its previous iteration, the Watchman 2.5, was published this year by Freeman et al. [37] who reported US LAAC registry outcomes from 54,206 patients (mean age 76 years; 59% men) undergoing LAAC with the new Watchman FLX (n = 27,103) versus previous Watchman 2.5 (n = 27,103). In-hospital major adverse events were significantly lower with the new Watchman FLX (1.35% vs. 2.4%, OR 0.57: 95% CI 0.50–0.65) driven by reductions in pericardial effusion requiring intervention (0.42% vs. 1.23%), device embolization (0.02 vs. 0.06%) and major bleeding (1.08% vs. 2.05%). Longer follow-up will help clarify if technical aspects between devices confer long-term clinical outcome advantages.

Despite the evolution of device technology for LAAC, key clinical questions, such as anticoagulation strategy, remain. Freeman et al. conducted a US LAAC registry analysis of 31,994 patients who underwent Watchman LAAC between 2016 and 2018. Only 12.2% of patients received the full anticoagulation protocol mandated by clinical trials [38] (Fig. 3). In contrast to previous European reports from EWOLUTION (Registry on WATCHMAN Outcomes in Real-Life Utilization), the 45-day adjusted adverse event rate was longer if discharged on warfarin alone (HR 0.692; 95% CI 0.569–0.841) or DOAC alone (HR 0.731; 95% CI 0.574–0.930) versus warfarin plus aspirin, suggesting that further research is needed to guide the optimal antithrombotic strategy post-LAAC.

Fig. 3

Post-Watchman implantation antithrombotic strategies and associated risk of adverse outcomes. The most common strategy was warfarin plus aspirin. The lowest risk of adverse events was seen in groups anticoagulated with either warfarin or NOAC alone (primarily driven by reduced bleeding rates). Interestingly, there was no difference in ischaemia stroke or device-related thrombus between groups. Reproduced with the kind permission of the Journal of the American College of Cardiology [38]

Acute Coronary Syndromes

The ISCHAEMIA trial (Initial Invasive or Conservative Strategy for Stable Coronary Disease) was a previously reported that routine invasive therapy versus optimal medical therapy (OMT) in stable patients with moderate ischaemia did not reduce major adverse events (MAE), but the possibility of excess events over longer follow-up was queried. The ISCHAEMIA-EXTEND study (median follow-up 5.7 years) [39] reported that while there was still no difference in all-cause mortality in routine invasive versus medical therapy (12.7% vs. 13.4%, P = 0.74), after 2 years the survival curves for cardiovascular (CV) death started to diverge and by 7 years were significantly lower in the routine invasive group (6.4% vs. 8.6% HR 0.78; 95% CI 0.63, 0.96). Conversely, there was an increase in non-CV death in the routine invasive group (5.5% vs. 4.4%, HR 1.44; 95% CI 1.08–1.91). On balance, this still supports an initial OMT strategy but highlights the utility of understanding anatomy to risk stratify and perhaps identify those patients who will benefit the most from CV risk reduction (Fig. 4). Ten-year follow-up data will prove informative.

Fig. 4

Kaplan–Meier survival Curves demonstrating cumulative event rate of all-cause mortality and CV mortality at 8 years in the ISCHAEMIA-EXTEND trial. Notably, a lower 7-year rate CV mortality was demonstrated in the invasive group [6.4% vs. 8.6%; adjusted hazard ratio, 0.78 (95% CI, 0.63–0.96)]; however, there was no difference in all-cause mortality [7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 (95% CI, 0.85–1.18)] [