Contemporary outcomes of chronic total occlusion percutaneous coronary intervention in Europe: the ERCTO registry.

BACKGROUND: Percutaneous coronary interventions (PCI) of chronic total occlusions (CTO) have reached high procedural success rates thanks to dedicated equipment, evolving techniques, and worldwide adoption of state-of-the-art crossing algorithms. AIMS: We report the contemporary results of CTO PCIs performed by a large European community of experienced interventionalists. Furthermore, we investigated the impact of different risk factors for procedural major adverse cardiac and cerebrovascular events (MACCE) and trends of employment of specific devices like dual lumen microcatheters, guiding catheter extensions, intravascular ultrasound and calcium-modifying tools. METHODS: We evaluated data from 8,673 CTO PCIs included in the European Registry of Chronic Total Occlusion (ERCTO) between January 2021 and October 2022. RESULTS: The overall technical success rate was 89.1% and was higher in antegrade as compared with retrograde cases (92.8% vs 79.3%; p<0.001). Compared with antegrade procedures, retrograde procedures had a higher complexity of attempted lesions (Japanese CTO [J-CTO] score: 3.0±1.0 vs 1.9±1.2; p<0.001), a higher procedural and in-hospital MACCE rate (3.1% vs 1.2%; p<0.018) and a higher perforation rate with and without tamponade (1.5% vs 0.4% and 8.3% vs 2.1%, respectively; p<0.001). As compared with mid-volume operators, high-volume operators had a higher technical success rate in antegrade and retrograde procedures (93.4% vs 91.2% and 81.5% vs 69.0%, respectively; p<0.001), and had a lower MACCE rate (1.47% vs 2.41%; p<0.001) despite a higher mean complexity of the attempted lesions (J-CTO score: 2.42±1.28 vs 2.15±1.27; p<0.001). CONCLUSIONS: The adoption of different recanalisation techniques, operator experience and the use of specific devices have contributed to a high procedural success rate despite the high complexity of the lesions documented in the ERCTO.

CTO and Bifurcation Lesions: An Expert Consensus From the European Bifurcation Club and EuroCTO Club.

Knowledge in the field of bifurcation lesions and chronic total occlusions (CTOs) has progressively improved over the past 20 years. Therefore, the European Bifurcation Club and the EuroCTO Club have decided to write a joint consensus statement to share general knowledge and practical approaches in this complex field. When percutaneously treating CTOs, bifurcation lesions with relevant side branches (SBs) are found in approximately one-third of cases (35% at the proximal cap, 38% at the distal cap, and 27% within the CTO body). Occlusion of a relevant SB is not rare and has been shown to be associated with procedural complications and adverse outcomes. Simple bifurcation rules are very useful to prevent SB occlusion, and provisional SB stenting is the recommended approach in the majority of cases: protect the SB as soon as possible by wiring it, respect the fractal anatomy of the bifurcation by using the 3-diameter rule, and avoid using dissection and re-entry techniques. A systematic 2-stent approach can be used if needed or sometimes to connect both branches of the bifurcation. The retrograde approach can be very useful to save a relevant SB, especially in the case of a bifurcation at the distal cap or within the CTO body. Intravascular ultrasound is also a very important tool to address the difficulties with bifurcations at the proximal or distal cap and sometimes also within the CTO segment. Double-lumen microcatheters and angulated microcatheters are crucial tools to resolve access difficulties to the SB or the main branch.

Gender differences in percutaneous coronary intervention for chronic total occlusions from the ERCTO study.

BACKGROUND: Gender-specific data addressing percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) in female patients are scarce and based on small sample size studies. AIMS: We aimed to analyze gender-differences regarding in-hospital clinical outcomes after CTO-PCI. METHODS: Data from 35,449 patients enrolled in the prospective European Registry of CTOs were analyzed. The primary outcome was the comparison of procedural success rate in the two cohorts (women vs. men), defined as a final residual stenosis less than 20%, with Thrombolysis In Myocardial Infarction grade flow = 3. In-hospital major adverse cardiac and cerebrovascular events (MACCEs) and procedural complications were deemed secondary outcomes. RESULTS: Women represented 15.2% of the entire study population. They were older and more likely to have hypertension, diabetes, and renal failure, with an overall lower J-CTO score. Women showed a higher procedural success rate (adjusted OR [aOR] = 1.115, confidence interval [CI]: 1.011-1.230, p = 0.030). Apart from previous myocardial infarction and surgical revascularization, no other significant gender differences were found among predictors of procedural success. Antegrade approach with true-to-true lumen techniques was more commonly used than retrograde approach in females. No gender differences were found regarding in-hospital MACCEs (0.9% vs. 0.9%, p = 0.766), although a higher rate of procedural complications was observed in women, such as coronary perforation (3.7% vs. 2.9%, p < 0.001) and vascular complications (1.0% vs. 0.6%, p < 0.001). CONCLUSIONS: Women are understudied in contemporary CTO-PCI practice. Female sex is associated with higher procedural success after CTO-PCI, yet no sex differences were found in terms of in-hospital MACCEs. Female sex was associated with a higher rate of procedural complications.

Low-molecular-weight heparin in radial artery occlusion treatment: the LOW-RAO randomized study.

Radial artery occlusion (RAO) is the commonest complication of transradial catheterization. There is no evidence-based therapy, in the frame of a randomized control study, for the treatment of RAO. The purpose of the LOW-RAO study is to question the hypothesis if low-molecular-weight heparin is effective in the treatment of RAO after transradial coronary catheterization (both angiography and percutaneous coronary intervention). It is a prospective, open label, randomized controlled trial that will randomize 60 patients with RAO, irrespective of symptoms, into two groups, one receiving anticoagulation with low-molecular-weight heparin and the other receiving no treatment. The primary end point is improvement in radial artery patency rate at 4 weeks after the procedure. Clinical trial registration number: NCT04196309 (ClinicalTrials.gov).

Lay abstract Coronary angiogram, a procedure to check if there is any blockage in the heart's blood vessels, is often performed nowadays through a vessel in the wrist, called radial artery. One of the commonest risks of this procedure is the blockage of the radial artery afterward. This could go totally unnoticed; however, it may cause pain, tingling and numbness feeling in the fingers, loss of handgrip power and inability to use the artery for medical reasons in the future. Since there is no definite treatment for this situation up to now, the purpose of the LOW-RAO study is to try to find a solution for this problem. Patients diagnosed with radial artery blockage, will randomly receive for up to 4 weeks an injection that contains a blood-thinner, called low-molecular-weight heparin and is believed to be able to reopen the blocked radial artery. All patients will be regularly followed-up with ultrasounds for a month to check any progress with the blockage.

Shockwave Coronary Intravascular Lithotripsy System for Heavily Calcified De Novo Lesions and the Need for a Cost-Effectiveness Analysis.

The optimal management for severely calcified coronary artery disease is multi-adjunctive. Different strategies with dedicated devices should be available in the cardiac catheterization laboratory with their selection depending on the nature of the calcific disease and its anatomical distribution. Shockwave Intravascular Lithotripsy (S-IVL) system offers a novel option for lesion preparation of heavily calcified plaques in coronary and peripheral vessels. S-IVL is based on the fundamental principles of lithotripsy, a technology that has been used to modify renal stones for over 30 years. Pulsatile mechanical energy is used to fragment selectively amorphous calcium, sparing soft tissue. S-IVL has the potential of more widespread adoption because of its proven safety, efficacy and operational simplicity, but cost-effectiveness of such advanced technology will need to be analyzed.

Atrial fibrillation risk in patients suffering from type I diabetes mellitus. A review of clinical and experimental evidence.

Atrial fibrillation (AF) and diabetes mellitus (DM) are commonly encountered in clinical practice. Although, the long term macrovascular and microvascular sequela of DM are well validated, the association between the less prevalent type 1 DM (T1DM) and atrial arrhythmogenesis is poorly understood. In the present review we highlight the current experimental and clinical data addressing this complex interaction. Animal studies support that T1DM, characterized by insulin deficiency and glycemic variability, impairs phosphatidylinositol 3­kinase (PI3K)/protein kinase B signaling pathway. This pathway holds a central role in atrial electrical and structural remodeling responsible for arrhythmia initiation and maintenance. The molecular ''footprint'' of T1DM in atrial myocytes seems to involve a state of increased oxidative stress, impaired glucose transportation, ionic channel dysregulation and eventually fibrosis. On the contrary only a few clinical studies have examined the role of T1DM as an independent risk factor for AF development, and are discussed here. Further research is needed to solidify the real magnitude of this association and to investigate the clinical implications of PI3K molecular signaling pathway in atrial fibrillation management.

Greater decline of acute stroke admissions compared with acute coronary syndromes during COVID-19 outbreak in Greece: Cerebro/cardiovascular implications amidst a second wave surge.

BACKGROUND AND PURPOSE: A remarkable decline in admissions for acute stroke and acute coronary syndrome (ACS) has been reported in countries severely hit by the COVID-19 pandemic. However, limited data are available from countries with less COVID-19 burden focusing on concurrent stroke and ACS hospitalisation rates from the same population. METHODS: The study was conducted in three geographically and demographically representative COVID-19 referral university hospitals in Greece. We recorded the rate of stroke and ACS hospital admissions during a 6-week period of the COVID-19 outbreak in 2020 and compared them with the rates of the corresponding period in 2019. RESULTS: We found a greater relative reduction of stroke admissions (51% [35 vs. 71]; incidence rate ratio [IRR]: 0.49, p = 0.001) compared with ACS admissions (27% [123 vs. 168]; IRR: 0.73, p = 0.009) during the COVID-19 outbreak (p = 0.097). Fewer older (>65 years) patients (stroke: 34.3% vs. 45.1%, odds ratio [OR]: 0.64, p = 0.291; ACS: 39.8% vs. 54.2%, OR: 0.56, p = 0.016) were admitted during the COVID-19 compared with the control period. CONCLUSIONS: Hospitalisation rates both for stroke and ACS were reduced during the COVID-19 outbreak in a country with strict social distancing measures, low COVID-19 incidence and low population mortality. Lack of triggers for stroke and ACS during social distancing/quarantining may explain these observations. However, medical care avoidance attitudes among cerebro/cardiovascular patients should be dissipated amidst the rising second COVID-19 wave.

Intracoronary thrombolysis and stentless primary percutaneous coronary intervention in an ectatic right coronary artery with large thrombus burden.

A 58-year-old man was admitted to our center with an inferior ST-segment elevation myocardial infarction. A coronary angiogram showed an ectatic right coronary artery (RCA) occluded at mid vessel by a significant clot burden quantified by micro-computed tomography. Guide catheter-directed intracoronary thrombolysis with low-dose tenekteplase resulted in regaining RCA flow, when numerous efforts of manual and 'mother-child' thrombectomy had failed to achieve. A stentless strategy was followed with final thrombolysis in myocardial infarction 3 flow and angiographically insignificant stenosis remaining in the RCA. The combination of intracoronary thrombolysis and a stentless strategy is a safe and effective treatment in ST-segment elevation myocardial infarction patients with ectatic arteries and large thrombus burden when repeat manual aspiration thrombectomy fails.

Risk for Recurrent Cardiovascular Events and Expected Risk Reduction With Optimal Treatment 1 Year After an Acute Coronary Syndrome.

According to the latest European Society of Cardiology Guidelines for the diagnosis and management of chronic coronary syndromes, patients who suffered an acute coronary syndrome fall into a chronic stable phase after 1 year. In these patients, the estimated 10-year risk for recurrent cardiovascular events varies considerably. We applied the SMART (Second Manifestations of Arterial Disease) risk score in 281 patients 1 year after an acute coronary syndrome to estimate the 10-year risk for recurrent cardiovascular events (subsequent nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). We assessed the distribution of the estimated risk and the potential risk reduction that might be achieved with optimal guideline-directed management of modifiable risk factors (systolic blood pressure, low-density lipoprotein cholesterol, smoking, and body mass index). In our cohort, the median SMART score was 16.1% (interquartile range [IQR] 9.7 to 27.3), particularly increased in patients with older age, diabetes, polyvascular disease or chronic kidney disease (median 28.6%, IQR 20.8 to 52.9; 23.8%, 4.8 to 41.6; 29.4%, 18.8 to 49.7; 53.8%, 26.5 to 71.6, respectively). If all modifiable risk factors met guideline-recommended targets, the median SMART risk score would be 9.6% (IQR 6.3 to 20.9), with 51% of the patients at a 10-year risk <10%, while 11% and 15% at 20% to 30% and >30% risk, respectively. In conclusion, the SMART score had a wide distribution in patients with chronic coronary syndromes. A quarter of patients remained at a >20% 10-year risk, even with optimal risk factor management, clearly underlining that residual risk is an unmet clinical challenge.

"Missing" acute coronary syndrome hospitalizations during the COVID-19 era in Greece: Medical care avoidance combined with a true reduction in incidence?

BACKGROUND: Reports from countries severely hit by the COVID-19 pandemic suggest a decline in acute coronary syndrome (ACS)-related hospitalizations. The generalizability of this observation on ACS admissions and possible related causes in countries with low COVID-19 incidence are not known. HYPOTHESIS: ACS admissions were reduced in a country spared by COVID-19. METHODS: We conducted a nationwide study on the incidence rates of ACS-related admissions during a 6-week period of the COVID-19 outbreak and the corresponding control period in 2019 in Greece, a country with strict social measures, low COVID-19 incidence, and no excess in mortality. RESULTS: ACS admissions in the COVID-19 (n = 771) compared with the control (n = 1077) period were reduced overall (incidence rate ratio [IRR]: 0.72, P < .001) and for each ACS type (ST-segment elevation myocardial infarction [STEMI]: IRR: 0.76, P = .001; non-STEMI: IRR: 0.74, P < .001; and unstable angina [UA]: IRR: 0.63, P = .002). The decrease in STEMI admissions was stable throughout the COVID-19 period (temporal correlation; R2 = 0.11, P = .53), whereas there was a gradual decline in non-STEMI/UA admissions (R2 = 0.75, P = .026) following the progressively stricter social measures. During the COVID-19 period, patients admitted with ACS presented more frequently with left ventricular systolic impairment (22.2 vs 15.5% control period; P < .001). CONCLUSIONS: We observed a reduction in ACS hospitalizations during the COVID-19 outbreak in a country with strict social measures, low community transmission, and no excess in mortality. Medical care avoidance behavior is an important factor for these observations, while a true reduction of the ACS incidence due to self-isolation/quarantining may have also played a role.

Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial.

Importance: Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic. Low-dose colchicine combines anti-inflammatory action with a favorable safety profile. Objective: To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19). Design, Setting, and Participants: In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece. Intervention: Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks. Main Outcomes and Measures: Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death. Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events. The primary efficacy analysis was performed on an intention-to-treat basis. Results: A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. Median (interquartile range) peak high-sensitivity cardiac troponin values were 0.0112 (0.0043-0.0093) ng/mL in the control group and 0.008 (0.004-0.0135) ng/mL in the colchicine group (P = .34). Median (interquartile range) maximum C-reactive protein levels were 4.5 (1.4-8.9) mg/dL vs 3.1 (0.8-9.8) mg/dL (P = .73), respectively. The clinical primary end point rate was 14.0% in the control group (7 of 50 patients) and 1.8% in the colchicine group (1 of 55 patients) (odds ratio, 0.11; 95% CI, 0.01-0.96; P = .02). Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = .03). Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [45.5%] vs 9 patients [18.0%]; P = .003). Conclusions and Relevance: In this randomized clinical trial, participants who received colchicine had statistically significantly improved time to clinical deterioration. There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels. These findings should be interpreted with caution. Trial Registration: ClinicalTrials.gov Identifier: NCT04326790.

Differences in patients and lesion and procedure characteristics depending on the age of the coronary chronic total occlusion.

INTRODUCTION: Whether duration of chronic total occlusion (CTO) affects lesion and procedural characteristics remains largely unknown. AIM: To investigate whether CTO duration influences lesion characteristics and revascularization success. MATERIAL AND METHODS: EuroCTO Registry data on patients who had CTO percutaneous coronary intervention between January 2015 and April 2017 were analyzed. Three groups were created based on occlusion age: 3 to 6 months (n = 1415), 7 to 12 months (n = 973), > 12 months (n = 1656). RESULTS: Patients with greater CTO duration were older (63.0 (56.0-70.0); 63.0 (56.0-71.0); 66.0 (59.0-73.0) years respectively; p < 0.001), had more 3-vessel disease (32.2%; 30.9%; 46.1% respectively; p < 0.001) and more frequent prior coronary artery bypass grafting (8.2%; 9.9%; 29.4% respectively; p < 0.001). In multivariate analysis, occlusion duration was associated with moderate/severe calcification (OR = 1.52; 95% CI: 1.28-1.80; p < 0.001), lesion length > 20 mm (OR 1.77; 95% CI 1.49-2.10; p < 0.001), and collateral circulation Werner type 2 (OR = 1.20; 95% CI: 1.01-1.43; p = 0.041). The CTO duration was associated with lower procedural success (OR for success 0.60; 95% CI: 0.46-0.79; p < 0.001). In multivariate analysis in-hospital adverse events did not differ according to duration of CTO. CONCLUSIONS: Coronary artery CTO duration is associated with greater extent of calcification, lesion length, development of collateral circulation and, most importantly, with lower procedural success.

Derivation and Validation of a Chronic Total Coronary Occlusion Intervention Procedural Success Score From the 20,000-Patient EuroCTO Registry: The EuroCTO (CASTLE) Score.

OBJECTIVES: The aim was to establish a contemporary scoring system to predict the outcome of chronic total occlusion coronary angioplasty. BACKGROUND: Interventional treatment of chronic total coronary occlusions (CTOs) is a developing subspecialty. Predictors of technical success or failure have been derived from datasets of modest size. A robust scoring tool could facilitate case selection and inform decision making. METHODS: The study analyzed data from the EuroCTO registry. This prospective database was set up in 2008 and includes >20,000 cases submitted by CTO expert operators (>50 cases/year). Derivation (n = 14,882) and validation (n = 5,745) datasets were created to develop a risk score for predicting technical failure. RESULTS: There were 14,882 patients in the derivation dataset (with 2,356 [15.5%] failures) and 5,745 in the validation dataset (with 703 [12.2%] failures). A total of 20.2% of cases were done retrogradely, and dissection re-entry was performed in 9.3% of cases. We identified 6 predictors of technical failure, collectively forming the CASTLE score (Coronary artery bypass graft history, Age (≥70 years), Stump anatomy [blunt or invisible], Tortuosity degree [severe or unseen], Length of occlusion [≥20 mm], and Extent of calcification [severe]). When each parameter was assigned a value of 1, technical failure was seen to increase from 8% with a CASTLE score of 0 to 1, to 35% with a score ≥4. The area under the curve (AUC) was similar in both the derivation (AUC: 0.66) and validation (AUC: 0.68) datasets. CONCLUSIONS: The EuroCTO (CASTLE) score is derived from the largest database of CTO cases to date and offers a useful tool for predicting procedural outcome.

A case of sarcoidosis-associated pulmonary hypertension masquerading as chronic thromboembolic pulmonary hypertension.

Occlusive vasculopathy due to the development and accumulation of granulomas at the level of intima of large vessels, as well as mediastinal lymph nodes and fibrosing mediastinitis secondary to sarcoidosis, causing extrinsic compression of mediastinal vascular structure are uncommon mechanisms of sarcoidosis-associated pulmonary hypertension. We present a case of a 62-year-old woman with a rare manifestation of sarcoidosis, which was misclassified and treated as chronic thromboembolic pulmonary hypertension for a long period. Fluorine-18-fluorodeoxyglucose positron emission tomography played a major role in accessing final diagnosis. Mechanisms that lead to development of pulmonary hypertension, the contribution of novel imaging modalities, and treatment options are discussed.

Anti-Inflammatory Treatment With Colchicine in Acute Myocardial Infarction: A Pilot Study.

BACKGROUND: Inflammatory processes have been identified as key mediators of the deleterious effects of ischemia/reperfusion in ST-segment-elevation myocardial infarction. Colchicine is a substance with potent anti-inflammatory properties, suitable for safe use in patients with cardiovascular disease. The purpose of this study was to test the hypothesis that a short course of colchicine treatment could lead to reduced infarct size. METHODS AND RESULTS: Patients presenting with ST-segment-elevation myocardial infarction ≤12 hours from pain onset (treated with primary percutaneous coronary intervention) were randomly assigned to colchicine or placebo for 5 days. The primary outcome parameter was the area under the curve of creatine kinase-myocardial brain fraction concentration. A subset of patients underwent cardiac MRI with late gadolinium enhancement 6 to 9 days after the index ST-segment-elevation myocardial infarction. One hundred fifty-one patients were included (60 in the MRI substudy). The area under the creatine kinase-myocardial brain fraction curve was 3144 (interquartile range [IQR], 1754-6940) ng·h(-1)·mL(-1) in the colchicine group in comparison with 6184 (IQR, 4456-6980) ng·h(-1)·mL(-1) in controls (P<0.001). Indexed MRI-late gadolinium enhancement-defined infarct size was 18.3 (IQR, 7.6-29.9) mL/1.73 m(2) in the colchicine group versus 23.2 (18.5-33.4) mL/1.73 m(2) in controls (P=0.019). The relative infarct size (as a proportion to left ventricular myocardial volume) was 13.0 (IQR, 8.0-25.3) % and 19.8 (IQR, 13.7-29.8) %, respectively (P=0.034). CONCLUSIONS: These results suggest a potential benefit of colchicine in ST-segment-elevation myocardial infarction, but further clinical trials are necessary to draw secure conclusions, especially considering the fact that the present study was not powered to assess clinical end points. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936285.

Report of a European Society of Cardiology-European Association of Percutaneous Cardiovascular Interventions task force on the evaluation of coronary stents in Europe: executive summary.

The evaluation for European Union market approval of coronary stents falls under the Medical Device Directive that was adopted in 1993. Specific requirements for the assessment of coronary stents are laid out in supplementary advisory documents. In response to a call by the European Commission to make recommendations for a revision of the advisory document on the evaluation of coronary stents (Appendix 1 of MEDDEV 2.7.1), the European Society of Cardiology (ESC) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) established a Task Force to develop an expert advisory report. As basis for its report, the ESC-EAPCI Task Force reviewed existing processes, established a comprehensive list of all coronary drug-eluting stents that have received a CE mark to date, and undertook a systematic review of the literature of all published randomized clinical trials evaluating clinical and angiographic outcomes of coronary artery stents between 2002 and 2013. Based on these data, the TF provided recommendations to inform a new regulatory process for coronary stents. The main recommendations of the task force include implementation of a standardized non-clinical assessment of stents and a novel clinical evaluation pathway for market approval. The two-stage clinical evaluation plan includes recommendation for an initial pre-market trial with objective performance criteria (OPC) benchmarking using invasive imaging follow-up leading to conditional CE-mark approval and a subsequent mandatory, large-scale randomized trial with clinical endpoint evaluation leading to unconditional CE-mark. The data analysis from the systematic review of the Task Force may provide a basis for determination of OPC for use in future studies. This paper represents an executive summary of the Task Force's report.