European position paper on the management of patients with patent foramen ovale. Part II - Decompression sickness, migraine, arterial deoxygenation syndromes and select high-risk clinical conditions.

Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.

Percutaneous closure of a patent foramen ovale causing exercise hypoxemia: Case report and a review of the literature.

Provoked exercise desaturation is a rare presentation of patent foramen ovale (PFO), when vigorous exercise leads to desaturation of arterial blood and subsequent dyspnea. We present a case of provoked exercise desaturation and curative percutaneous closure and review the literature. A 54-year-old male patient presented with shortness of breath during exercise in the pneumology outpatient department. During exercise spirometry, a relevant drop in arterial oxygen saturation and partial pressure of oxygen was observed and a right-left shunt suspected. In a transesophageal echocardiogram, a PFO was observed. Cardiac catheterization documented a right-left-shunt causing desaturation during exercise. Following percutaneous closure of the PFO, exercise induced desaturation was no longer detectable during exercise spirometry and there was considerable improvement in exercise capacity and subjective dyspnea. To sum up, provoked exercise desaturation is a rare but curable presentation of PFO. Percutaneous closure is a safe and effective way to treat this entity.

Amplatzer left atrial appendage closure: Single versus combined procedures.

OBJECTIVES: This study compares procedural and late clinical outcomes of left atrial appendage closure (LAAC) with Amplatzer devices as a single versus a combined procedure with other structural or coronary interventions. BACKGROUND: Multiple cardiac conditions are frequent among elderly patients and invite simultaneous treatment to ensure a favorable patient outcomes. METHODS: 559 consecutive patients (73.3 ± 11.1 years) underwent LAAC with Amplatzer devices at two centres (Bern and Zurich university hospitals, Switzerland) either as a single procedure or combined with other interventions. The primary safety endpoint was a composite of major peri-procedural complications and major bleeding at follow-up, the primary efficacy endpoint included stroke, systemic embolism, and cardiovascular/unexplained death. All event rates are reported per 100 patient-years. RESULTS: In 263 single and 296 combined procedures with percutaneous coronary interventions (47.6%), closure of an atrial septal defect (8.4%) or a patent foramen ovale (36.5%), transcatheter aortic valve implantation (10.1%), mitral clipping (4.1%), atrial fibrillation ablation (8.8%), or another procedure (3.0%) were analyzed. Device success (96.6% [single] vs. 99.0% [combined], p = .08) did not differ between the groups. After a mean follow-up of 2.6 ± 1.5 vs. 2.5 ± 1.5 years and a total of 1,422 patient-years, the primary efficacy (40/677, 5.9% [single] vs. 37/745, 5.0% [combined]; HR, 1.2, 95% CI, 0.8-1.9, p = .44), as well as the primary safety endpoint (25/677, 3.7% vs 28/745, 3.8%; HR, 1.0, 95% CI, 0.6-1.8, p = .89) were comparable. CONCLUSIONS: LAAC with Amplatzer devices combined with structural, coronary, and electrophysiological procedures offers procedural feasibility and safety, as well as long-term efficacy.

Single antiplatelet therapy with use of prasugrel in patients undergoing percutaneous coronary intervention.

OBJECTIVES: We aimed to assess the ischemic and bleeding risks of single antiplatelet therapy (SAPT) with prasugrel compared with standard dual antiplatelet therapy (DAPT) (aspirin plus clopidogrel for 1 year) in patients with chronic coronary syndrome (CCS) treated with new generation drug-eluting stents (DES). BACKGROUND: To date, data on SAPT with potent P2Y12 inhibitors in the absence of aspirin immediately after PCI are limited. METHODS: Between January 2009 and November 2019, all CCS patients undergoing percutaneous coronary intervention (PCI) enrolled to the Bern PCI registry were considered for analysis. We performed propensity score matching in a 1:4 fashion to compare patients who received SAPT with prasugrel versus standard DAPT. The primary ischemic endpoint was a composite of cardiovascular death, myocardial infarction, and stroke and the primary bleeding endpoint was BARC 3 or 5 bleeding, both assessed at 1 year. RESULTS: After propensity score matching, the final study population consisted of 225 patients with SAPT and 889 with DAPT. There was no significant difference in rates of the primary ischemic (5.2% vs. 4.2%, p = .50) or the primary bleeding (1.5% vs. 2.0%, p = .60) endpoints between groups. SAPT was not associated with an increased risk of definite stent thrombosis (0.9% vs. 0.8%, p = .83). CONCLUSIONS: Among selected CCS patients undergoing PCI with DES, SAPT with prasugrel was not associated with an excess of ischemic events compared with standard DAPT. No difference in bleeding was observed either. The results may serve as the basis for larger trials assessing the potential benefits and risks of SAPT.

Impact of individual stroke risk on outcome after Amplatzer left atrial appendage closure in patients with atrial fibrillation.

OBJECTIVES: To investigate periprocedural and long-term outcome of left atrial appendage closure (LAAC) using Amplatzer occluders with respect to individual pre-procedural stroke risk. BACKGROUND: LAAC is a proven strategy for prevention from stroke and bleeding in patients with nonvalvular atrial fibrillation not amenable to oral anticoagulation. Whether individual pre-procedural stroke risk may affect procedural and long-term clinical outcome after LAAC is unclear. METHODS: Multicenter study of consecutive patients who underwent Amplatzer-LAAC. Using pre-procedural CHADS2 score, outcomes were compared between a low (0-2 points) and a high stroke risk group (3-6 points). RESULTS: Five hundred consecutive patients (73.9 ± 10.1 years) who underwent Amplatzer-LAAC. Two hundred and forty eight had preprocedural CHADS2 score ≤ 2 points (low-risk group) and the remaining 252 patients had 3-6 points (high-risk group). Periprocedural complication rates (6.0% vs. 5.6%, p = .85), procedural success (LAAC without major periprocedural or device-related complications or major para-device leaks: 89.4% vs. 87.9%, p = .74), and 30-day-mortality (2.4% vs. 2.6%, p = .77) were comparable. After 1,346 patient-years (PY), the long-term composite efficacy endpoint (stroke, systemic embolism, cardiovascular, and unexplained death) was reached in 23/653 (3.5/100 PY) versus 52/693 (7.5/100 PY); HR = 2.13; 95%-CI, 1.28-3.65, p = .002) with stroke rates 67% and 68% lower than anticipated by preprocedural CHADS2 score. Combined safety endpoint (major periprocedural complications and major, life-threatening or fatal bleedings) occurred in 22/653 (3.4/100 PY) versus 28/693 (4.0/100 PY); HR = 1.20; 95%-CI, 0.66-2.20, p = .52). CONCLUSIONS: Compared with patients at low risk of stroke, LAAC with Amplatzer devices is associated with similar safety and efficacy in high-risk patients in our study.

Heterogeneity of Treatment Effects in an Analysis of Pooled Individual Patient Data From Randomized Trials of Device Closure of Patent Foramen Ovale After Stroke.

Importance: Patent foramen ovale (PFO)-associated strokes comprise approximately 10% of ischemic strokes in adults aged 18 to 60 years. While device closure decreases stroke recurrence risk overall, the best treatment for any individual is often unclear. Objective: To evaluate heterogeneity of treatment effect of PFO closure on stroke recurrence based on previously developed scoring systems. Design, Setting, and Participants: Investigators for the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) Consortium pooled individual patient data from all 6 randomized clinical trials that compared PFO closure plus medical therapy vs medical therapy alone in patients with PFO-associated stroke, and included a total of 3740 participants. The trials were conducted worldwide from 2000 to 2017. Exposures: PFO closure plus medical therapy vs medical therapy alone. Subgroup analyses used the Risk of Paradoxical Embolism (RoPE) Score (a 10-point scoring system in which higher scores reflect younger age and the absence of vascular risk factors) and the PFO-Associated Stroke Causal Likelihood (PASCAL) Classification System, which combines the RoPE Score with high-risk PFO features (either an atrial septal aneurysm or a large-sized shunt) to classify patients into 3 categories of causal relatedness: unlikely, possible, and probable. Main Outcomes and Measures: Ischemic stroke. Results: Over a median follow-up of 57 months (IQR, 24-64), 121 outcomes occurred in 3740 patients. The annualized incidence of stroke with medical therapy was 1.09% (95% CI, 0.88%-1.36%) and with device closure was 0.47% (95% CI, 0.35%-0.65%) (adjusted hazard ratio [HR], 0.41 [95% CI, 0.28-0.60]). The subgroup analyses showed statistically significant interaction effects. Patients with low vs high RoPE Score had HRs of 0.61 (95% CI, 0.37-1.00) and 0.21 (95% CI, 0.11-0.42), respectively (P for interaction = .02). Patients classified as unlikely, possible, and probable using the PASCAL Classification System had HRs of 1.14 (95% CI, 0.53-2.46), 0.38 (95% CI, 0.22-0.65), and 0.10 (95% CI, 0.03-0.35), respectively (P for interaction = .003). The 2-year absolute risk reduction was -0.7% (95% CI, -4.0% to 2.6%), 2.1% (95% CI, 0.6%-3.6%), and 2.1% (95% CI, 0.9%-3.4%) in the unlikely, possible, and probable PASCAL categories, respectively. Device-associated adverse events were generally higher among patients classified as unlikely; the absolute risk increases in atrial fibrillation beyond day 45 after randomization with a device were 4.41% (95% CI, 1.02% to 7.80%), 1.53% (95% CI, 0.33% to 2.72%), and 0.65% (95% CI, -0.41% to 1.71%) in the unlikely, possible, and probable PASCAL categories, respectively. Conclusions and Relevance: Among patients aged 18 to 60 years with PFO-associated stroke, risk reduction for recurrent stroke with device closure varied across groups classified by their probabilities that the stroke was causally related to the PFO. Application of this classification system has the potential to guide individualized decision-making.

Risk of Paradoxical Embolism (RoPE)-Estimated Attributable Fraction Correlates With the Benefit of Patent Foramen Ovale Closure: An Analysis of 3 Trials.

BACKGROUND AND PURPOSE: In patients with cryptogenic stroke and patent foramen ovale (PFO), the Risk of Paradoxical Embolism (RoPE) Score has been proposed as a method to estimate a patient-specific "PFO-attributable fraction"-the probability that a documented PFO is causally-related to the stroke, rather than an incidental finding. The objective of this research is to examine the relationship between this RoPE-estimated PFO-attributable fraction and the effect of closure in 3 randomized trials. METHODS: We pooled data from the CLOSURE-I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack due to Presumed Paradoxical Embolism through a Patent Foramen Ovale), RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment), and PC (Clinical Trial Comparing Percutaneous Closure of Patent Foramen Ovale [PFO] Using the Amplatzer PFO Occluder With Medical Treatment in Patients With Cryptogenic Embolism) trials. We examine the treatment effect of closure in high RoPE score (≥7) versus low RoPE score (<7) patients. We also estimated the relative risk reduction associated with PFO closure across each level of the RoPE score using Cox proportional hazard analysis. We estimated a patient-specific attributable fraction using a PC trial-compatible (9-point) RoPE equation (omitting the neuroradiology variable), as well as a 2-trial analysis using the original (10-point) RoPE equation. We examined the Pearson correlation between the estimated attributable fraction and the relative risk reduction across RoPE strata. RESULTS: In the low RoPE score group (<7, n=912), the rate of recurrent strokes per 100 person-years was 1.37 in the device arm versus 1.68 in the medical arm (hazard ratio, 0.82 [0.42-1.59] P=0.56) compared with 0.30 versus 1.03 (hazard ratio, 0.31 [0.11-0.85] P=0.02) in the high RoPE score group (≥7, n=1221); treatment-by-RoPE score group interaction, P=0.12. The RoPE score estimated attributable fraction anticipated the relative risk reduction across all levels of the RoPE score, in both the 3-trial (r=0.95, P<0.001) and 2-trial (r=0.92, P<0.001) analyses. CONCLUSIONS: The RoPE score estimated attributable fraction is highly correlated to the relative risk reduction of device versus medical therapy. This observation suggests the RoPE score identifies patients with cryptogenic stroke who are likely to have a PFO that is pathogenic rather than incidental.

Long-term clinical outcomes of Amplatzer cardiac plug versus Amulet occluders for left atrial appendage closure.

OBJECTIVES: To compare long-term clinical outcomes after left atrial appendage closure with the Amplatzer Cardiac Plug (ACP) and Amulet. BACKGROUND: The Amulet was designed to improve clinical outcomes of first-generation ACP. METHODS: Three Amplatzer registries (Bern, Coburg, Zurich), with enrollment of patients from 2009 to 2018, were retrospectively analyzed. The primary safety endpoint was a composite of major peri-procedural complications and major bleedings, the primary efficacy endpoint included stroke, systemic embolism, and cardiovascular/unexplained death. The net clinical benefit was a combination of all above-mentioned hazards. RESULTS: A total of consecutive 563 patients (344 ACP vs. 219 Amulet) with a mean follow-up of 2.9 ± 1.6 and 1.9 ± 0.9 years were included. Mean age (74.4 ± 9.9 [ACP] vs. 74.4 ± 9.1 [Amulet] years), stroke (CHA2 DS2 -VASc score 4.4 ± 1.6 vs. 4.6 ± 1.7), and bleeding risk (HAS-BLED score 3.2 ± 1.1 vs. 3.2 ± 0.9) were comparable. The primary endpoints of efficacy (72/998, 7.2% [ACP] vs. 43/417, 10.3% [Amulet]; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.44-1.02, p = .062), safety (40/998, 4.0% vs. 18/417, 4.3%; HR, 1.15; 95% CI, 0.53-2.51, p = .72), and the net clinical benefit (101/998, 10.1% vs. 55/417, 13.4%; HR, 0.73; 95% CI, 0.49-1.07, p = .11) were similar. CONCLUSION: In the long term, left atrial appendage closure with first and second-generation Amplatzer devices provided similar efficacy, safety, and net clinical benefit. Clinical outcomes may be rather determined by implantation technique and hemodynamics, but not by the design modifications of the Amulet.

Clinical outcomes of Watchman vs. Amplatzer occluders for left atrial appendage closure (WATCH at LAAC).

AIMS: This study compares clinical outcomes of Watchman vs. Amplatzer devices for left atrial appendage closure (LAAC). METHODS AND RESULTS: Of two real-world registries, the Watchman registry Lichtenfels, Germany, and the Amplatzer registry Bern-Zurich, Switzerland, 303 and 333 consecutive patients, respectively, were included. After a 1:1 propensity score matching, 266 vs. 266 patients were compared by use of the predefined primary efficacy endpoint of stroke, systemic embolism and cardiovascular/unexplained death, the primary safety endpoint of major peri-procedural complications and major bleeding events at follow-up, and the combined hazard endpoint, a composite of all above-mentioned hazards. Mean age was 75.3 ± 7.8 (Watchman) vs. 75.1 ± 9.9 (Amplatzer) years, CHA2DS2-VASc score 4.5 ± 1.7 vs. 4.5 ± 1.5, and HAS-BLED score 3.2 ± 1.0 vs. 3.2 ± 1.0. At a mean follow-up of 2.4 ± 1.3 vs. 2.5 ± 1.5 years and 1.322 patient-years, the primary endpoints of efficacy [40/646, 6.2% [Watchman] vs. 43/676, 6.4% [Amplatzer]; hazard ratio (HR), 1.02; 95% confidence interval (CI), 0.66-1.58; P = 0.92] and safety (33/646, 5.1% vs. 30/676, 4.4%; HR, 0.57; 95% CI, 0.29-1.11; P = 0.10), as well as the combined hazard endpoint (69/646, 10.7% vs. 66/676, 9.8%; HR, 0.80; 95% CI, 0.55-1.12; P = 0.26) were similar for both groups. CONCLUSION: This study suggests comparable efficacy and safety of the Watchman and Amplatzer devices.

European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism.

The presence of a patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions; however, the subject remains controversial and no official statements have been published. This interdisciplinary paper, prepared with involvement of eight European scientific societies, aims to review the available trial evidence and to define the principles needed to guide decision making in patients with PFO. In order to guarantee a strict process, position statements were developed with the use of a modified grading of recommendations assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements of particular management options were weighed and graded according to predefined scales. Despite being based often on limited and non-randomised data, while waiting for more conclusive evidence, it was possible to conclude on a number of position statements regarding a rational general approach to PFO management and to specific considerations regarding left circulation thromboembolism. For some therapeutic aspects, it was possible to express stricter position statements based on randomised trials. This position paper provides the first largely shared, interdisciplinary approach for a rational PFO management based on the best available evidence.

Percutaneous patent foramen ovale closure during live case demonstrations.

BACKGROUND: Live case demonstrations serve as an educational tool for interventional techniques in cardiology. The aim of this study was to assess the safety and technical success of percutaneous patent foramen ovale (PFO) closure during live case demonstrations. METHODS: All patients who had undergone percutaneous PFO closure with Amplatzer devices during live case demonstrations at our institution were consecutively included in this retrospective analysis. Procedure related events were compared with summary event rates derived from the eight randomized controlled trials (RCTs) investigating PFO closure, as well as with a propensity matched cohort of patients treated under usual conditions. RESULTS: From April 2004 to June 2015, 142 patients underwent percutaneous PFO closure during live demonstrations, mainly for secondary prevention of cryptogenic cerebrovascular events. The interventions were fluoroscopy guided and successful in all but three cases (2%). Minor adverse events occurred in nine patients (6%). Contrast TEE performed at about 6 months showed complete closure in 84%. No significant differences with regard to technical success and major complications rate were found compared to RCTs, except for an increased rate of minor bleeding observed during live case demonstrations (P for difference < 0.001), mainly attributable to concomitant arterial access for incidental coronary angiography performed in 70% of patients. Except for slightly longer procedure duration, no difference was found compared to a matched population treated under usual conditions. CONCLUSION: Percutaneous PFO closure can be performed during live case demonstrations with the same high technical success as during routine cases.

[Myocardial bridging: a contemporary review]. / Le pont myocardique†: mise au point.

Myocardial bridging, corresponds to an abnormal, usually congenital, anatomical relationship between the myocardium and a coronary vessel. It most commonly affects the left anterior descending coronary artery. Despite technological advances, angiography remains the gold standard diagnostic method with a typical image of systolic compression (milking). Typically benign and asymptomatic, myocardial bridging can exceptionally be responsible for serious life threatening complications. Different therapeutic options may be considered, including pharmacological or interventional treatments. We present a clinical case and a review of the respective literature.

Le pont myocardique correspond à une anomalie coronaire, le plus souvent congénitale, dans sa relation anatomique par rapport au muscle myocardique qui touche plus fréquemment l'artère interventriculaire antérieure. Malgré les progrès techniques, l'angiographie demeure la méthode diagnostique de référence avec une image typique de compression systolique milking. Dans la plupart des cas bénigne et asymptomatique, elle peut néanmoins être responsable de complications sérieuses, voire fatales. Plusieurs alternatives thérapeutiques sont envisageables allant du traitement pharmacologique au traitement interventionnel. Le cas clinique présenté dans cet article nous a permis d'effectuer une revue de la littérature à ce sujet.

Interventional cardiology, where real life and science do not necessarily meet.

Evidence-based diagnosis, decision-making, and therapy appear a must these days. Generating and publishing evidence is a tedious job according to ever new and tightened research practice regulations. Rules will never prevent the typical human behaviour from showing the new thing to be shinier and the old thing dustier than they really are. The medical community is solicited to concoct a meal that is gullible for patients, authorities, and third-party payers out of the available evidence (after applying some conversion factors correcting the common bias of the researchers), anticipation of what will be the evidence tomorrow, common sense, and digested experience. Examples of misguidance by poorly produced or misinterpreted evidence are plentiful in interventional cardiology as they are in other disciplines. Coronary stents, for instance, were first underestimated due to the fact that they were generally used in bailout situations where the outcome remained rather dismal in spite of the salvaging potential of stents. Then they were overused quite uncritically rather to the detriment of the patient. Now with the high quality of the modern drug-eluting stents (DESs), the overuse persists but is no longer a concern. However, the enhanced potential of DESs compared with bare-metal stents was poorly exploited for >10 years because of reports that slipped through the meshes of good review and publication practice to convey the untenable message that bare-metal stents were preferable in many situations. As other examples, use of the fractional flow reserve (FFR) for decision-making has to be questioned despite prominently published reports recommending it. Fixing a lesion is today easier and hardly more complication prone than assessing it with the FFR. Closure of the patent foramen ovale may never be properly applied, because the collection of the understandably requested evidence takes decades, a follow-up duration that makes research unattractive to physicians and financiers. Transarterial aortic valve replacement, finally, is certain to eventually supplant surgical aortic valve replacement. However, this should have already been accomplished as a logical progress. The adoption of this remarkable breakthrough technology is slowed down by the quest for providing randomized evidence in patients, for whom the evidence should rather be derived from already existing studies, and by the quest to triage all these patients in a heart team, meaning to also keep the surgeons happy, although these patients do not really need them.

Percutaneous closure of patent foramen ovale: an underutilized prevention?

Stroke is a devastating event for patients and their families. Paradoxical embolism through a patent foramen ovale (PFO) is a recognized cause of stroke. Percutaneous PFO closure is a simple and safe procedure. The debate on PFO closure is far from settled. This is, in part, due to the fact that the three published randomized controlled trials (RCTs) on PFO closure vs. medical therapy were negative regarding their primary endpoint; however, as-treated and per-protocol analyses as well as several meta-analyses report a benefit of PFO closure. In our opinion, PFO closure is underutilized and the results of the three RCTs are not adequately reflected in the current guidelines.

Percutaneous closure of patent foramen ovale in migraine with aura, a randomized controlled trial.

AIMS: Migraine with aura and patent foramen ovale (PFO) are associated. The Percutaneous Closure of PFO in Migraine with Aura (PRIMA) trial is a multicentre, randomized trial to investigate the effect of percutaneous PFO closure in patients refractory to medical treatment. METHODS: Migraine with aura patients and PFO who were unresponsive to preventive medications were randomized to PFO closure or medical treatment. Both groups were given acetylsalicylic acid 75-100 mg/day for 6 months and clopidogrel 75 mg/day for 3 months. The primary endpoint was reduction in monthly migraine days during months 9-12 after randomization compared with a 3-month baseline phase before randomization. The committee reviewing the headache diaries were blinded to treatment assignment. RESULTS: One hundred and seven patients were randomly allocated to treatment with an Amplatzer PFO Occluder (N = 53) or control with medical management (N = 54). The trial was terminated prematurely because of slow enrolment. Eighty-three patients (40 occluder, 43 control) completed 12-month follow-up. Mean migraine days at baseline were 8 (±4.7 SD) in the closure group and 8.3 (±2.4) in controls. The primary endpoint was negative with -2.9 days after PFO closure vs. -1.7 days in control group (P = 0.17). Patent foramen ovale closure caused five adverse events without permanent sequelae. CONCLUSION: In patients with refractory migraine with aura and PFO, PFO closure did not reduce overall monthly migraine days.

Percutaneous coronary interventional strategies for treatment of in-stent restenosis: a network meta-analysis.

BACKGROUND: Percutaneous coronary intervention (PCI) with drug-eluting stents is the standard of care for treatment of native coronary artery stenoses, but optimum treatment strategies for bare metal stent and drug-eluting stent in-stent restenosis (ISR) have not been established. We aimed to compare and rank percutaneous treatment strategies for ISR. METHODS: We did a network meta-analysis to synthesise both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library Central Register of Controlled Trials, and Embase for randomised controlled trials published up to Oct 31, 2014, of different PCI strategies for treatment of any type of coronary ISR. The primary outcome was percent diameter stenosis at angiographic follow-up. This study is registered with PROSPERO, number CRD42014014191. FINDINGS: We deemed 27 trials eligible, including 5923 patients, with follow-up ranging from 6 months to 60 months after the index intervention. Angiographic follow-up was available for 4975 (84%) of 5923 patients 6-12 months after the intervention. PCI with everolimus-eluting stents was the most effective treatment for percent diameter stenosis, with a difference of -9·0% (95% CI -15·8 to -2·2) versus drug-coated balloons (DCB), -9·4% (-17·4 to -1·4) versus sirolimus-eluting stents, -10·2% (-18·4 to -2·0) versus paclitaxel-eluting stents, -19·2% (-28·2 to -10·4) versus vascular brachytherapy, -23·4% (-36·2 to -10·8) versus bare metal stents, -24·2% (-32·2 to -16·4) versus balloon angioplasty, and -31·8% (-44·8 to -18·6) versus rotablation. DCB were ranked as the second most effective treatment, but without significant differences from sirolimus-eluting (-0·2% [95% CI -6·2 to 5·6]) or paclitaxel-eluting (-1·2% [-6·4 to 4·2]) stents. INTERPRETATION: These findings suggest that two strategies should be considered for treatment of any type of coronary ISR: PCI with everolimus-eluting stents because of the best angiographic and clinical outcomes, and DCB because of its ability to provide favourable results without adding a new stent layer. FUNDING: None.

Percutaneous closure of patent foramen ovale in cryptogenic embolism.

BACKGROUND: The options for secondary prevention of cryptogenic embolism in patients with patent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale. We investigated whether closure is superior to medical therapy. METHODS: We performed a multicenter, superiority trial in 29 centers in Europe, Canada, Brazil, and Australia in which the assessors of end points were unaware of the study-group assignments. Patients with a patent foramen ovale and ischemic stroke, transient ischemic attack (TIA), or a peripheral thromboembolic event were randomly assigned to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy. The primary end point was a composite of death, nonfatal stroke, TIA, or peripheral embolism. Analysis was performed on data for the intention-to-treat population. RESULTS: The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group. The primary end point occurred in 7 of the 204 patients (3.4%) in the closure group and in 11 of the 210 patients (5.2%) in the medical-therapy group (hazard ratio for closure vs. medical therapy, 0.63; 95% confidence interval [CI], 0.24 to 1.62; P=0.34). Nonfatal stroke occurred in 1 patient (0.5%) in the closure group and 5 patients (2.4%) in the medical-therapy group (hazard ratio, 0.20; 95% CI, 0.02 to 1.72; P=0.14), and TIA occurred in 5 patients (2.5%) and 7 patients (3.3%), respectively (hazard ratio, 0.71; 95% CI, 0.23 to 2.24; P=0.56). CONCLUSIONS: Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT00166257.).

Percutaneous left atrial appendage occlusion: Effect of device positioning on outcome.

OBJECTIVE: The study in patients with percutaneous left atrial appendage (LAA) occlusion investigates clinical outcomes according to the position of the Amplatzer Cardiac Plug (ACP) disc. BACKGROUND: The ACP consists of a disc and an anchoring lobe. The disc is meant to cover the ostium of the LAA, but frequently retracts partially or completely into the neck of the LAA. It is not known whether a retracted disc affects outcome. METHODS: Outcomes of 169 consecutive patients (age 73.1 ± 10.4 years; 76% male) with successful LAA closure were analyzed according to the position of the ACP disc: group A had complete coverage of the LAA ostium; in group B the disc prolapsed partially or completely into the LAA-neck. Transesophageal echocardiography was performed 1-6 months after ACP implantation. The safety endpoint was the composite of clinically significant pericardial effusion, device embolization, procedure-related stroke/transient ischemic attack (TIA), major bleeding, or device thrombus. The efficacy endpoint was the composite of death, neurological events (ischemic and hemorrhagic stroke, TIA), or systemic embolism during follow-up. RESULTS: Group A comprised 76 patients (age 73.0 ± 9.9 years; 74% male) and group B 93 patients (age 73.3 ± 10.9 years; 79% male). Mean CHA2 DS2 -Vasc score and HASBLED score were 4.2 ± 1.7 (group A 4.3 ± 1.6; group B 4.2 ± 1.8) and 2.9 ± 1.1 (group A 2.9 ± 1.0; group B 3.0 ± 1.2), respectively. Mean follow-up of the study population was 13.0 ± 10.4 months. Overall, the composite safety and efficacy endpoints occurred in 20 (12%) and 6 patients (4%), respectively. There was no significant difference between groups A and B in the occurrence of the safety endpoint (13% vs. 11%, P = 0.64), or the efficacy endpoint (4% vs. 3%, P = 1.0). CONCLUSIONS: No evidence for a difference in the occurrence of the safety and efficacy endpoint was found between patients with complete vs. incomplete ACP disc coverage of the LAA ostium. The risk of repositioning attempts in case of incomplete coverage does not seem to be warranted. Current findings need further confirmation in a larger scale clinical trial. © 2016 Wiley Periodicals, Inc.

First generation versus second generation drug-eluting stents for the treatment of bifurcations: 5-year follow-up of the LEADERS all-comers randomized trial.

BACKGROUND: Historically, percutaneous coronary intervention (PCI) of bifurcation lesions was associated with worse procedural and clinical outcomes when compared with PCI of non-bifurcation lesions. Newer generation drug-eluting stents (DES) might improve long-term clinical outcomes after bifurcation PCI. METHODS AND RESULTS: The LEADERS trial was a 10-center, assessor-blind, non-inferiority, all-comers trial, randomizing 1,707 patients to treatment with a biolimus A9(TM) -eluting stent (BES) with an abluminal biodegradable polymer or a sirolimus-eluting stent (SES) with a durable polymer (ClinicalTrials.gov Identifier: NCT00389220). Five-year clinical outcomes were compared between patients with and without bifurcation lesions and between BES and SES in the bifurcation lesion subgroup. There were 497 (29%) patients with at least 1 bifurcation lesion (BES = 258; SES = 239). At 5-year follow-up, the composite endpoint of cardiac death, myocardial infarction (MI) and clinically-indicated (CI) target vessel revascularization (TVR) was observed more frequently in the bifurcation group (26.6% vs. 22.4%, P = 0.049). Within the bifurcation lesion subgroup, no differences were observed in (cardiac) death or MI rates between BES and SES. However, CI target lesion revascularization (TLR) (10.1% vs. 15.9%, P = 0.0495), and CI TVR (12.0% vs. 19.2%, P = 0.023) rates were significantly lower in the BES group. Definite/probable stent thrombosis (ST) rate was numerically lower in the BES group (3.1% vs. 5.9%, P = 0.15). Very late (>1 year) definite/probable ST rates trended to be lower with BES (0.4% vs. 3.1%, P = 0.057). CONCLUSIONS: In the treatment of bifurcation lesions, use of BES led to superior long-term efficacy compared with SES. Safety outcomes were comparable between BES and SES, with an observed trend toward a lower rate of very late definite/probable ST between 1 and 5 years with the BES. © 2015 Wiley Periodicals, Inc.