EURObservational Research Programme: a bibliometric assessment of its scientific output.

AIMS: Given the lack of reliable observational data, a network of volunteer centres, and standardized methodological procedures, the European Society of Cardiology EURObservational Research Programme (EORP) was set up to provide a better understanding of real-world cardiovascular care and outcomes. We aimed to evaluate the scientific impact of EORP using a bibliometric approach. METHODS AND RESULTS: We collected data for each individual publication and for each individual journal with at least one EORP publication. Bibliometric indicators evaluating research performance were categorized into those evaluating EORP publications (publication-based indicators) and those assessing the journals where those papers were published (journal-based indicators). During the first ∼11 years since its inception, we found that EORP produced 189 publications, with most published in journals in the first quartile (60.9%) or the second quartile (33.5%) of the Web of Science Journal Citation Report. The total number of citations to EORP publications was 9630 (average citation per publication of 51, h-index of 54, and 29 EORP publications with ≥100 citations). Of EORP publications, 20 had an Altmetric Attention Score >50 and 9 had a score >100. A total of 52 EORP papers have been cited 65 times in ESC Clinical Practice Guidelines between 2013 and 2021. CONCLUSION: EORP registries have contributed to impactful scientific knowledge. The high-quality metrics highlight the relevance of the EORP international cardiovascular registries to the academic community. Efforts are needed to support this, and other programmes aimed at delivering real-world evidence from independent patient data of cardiovascular care and outcomes across multiple geographies.

Multi-modality imaging assessment of native valvular regurgitation: an EACVI and ESC council of valvular heart disease position paper.

Valvular regurgitation represents an important cause of cardiovascular morbidity and mortality. Imaging is pivotal in the evaluation of native valve regurgitation and echocardiography is the primary imaging modality for this purpose. The imaging assessment of valvular regurgitation should integrate quantification of the regurgitation, assessment of the valve anatomy and function, and the consequences of valvular disease on cardiac chambers. In clinical practice, the management of patients with valvular regurgitation largely relies on the results of imaging. It is crucial to provide standards that aim at establishing a baseline list of measurements to be performed when assessing native valve regurgitation. The present document aims to present clinical guidance for the multi-modality imaging assessment of native valvular regurgitation.

Percutaneous mitral valve repair in severe secondary mitral regurgitation: Analysis of index hospitalization and economic evaluation based on the MITRA-FR trial.

BACKGROUND: Percutaneous mitral valve repair (pMVR) is reimbursed in France for severe secondary mitral regurgitation (SMR), but French data regarding the hospitalization index stay are lacking. AIMS: Our objectives were to describe the index hospitalization stay and to evaluate the cost of hospital stay for pMVR used in SMR. METHODS: A secondary evaluation based on patients who were randomized to the intervention group of the MITRA-FR study was undertaken. The economic evaluation was conducted according to the French hospital perspective. Medical resource use was estimated using specific data collected from patients enrolled in the MITRA-FR study and non-specific data from national statistics. RESULTS: The population was represented by 144 patients who underwent pMVR at 33 French centres. There was a mean±standard deviation of 7.9±1.5 hospital staff during procedures. The mean procedure duration was 154±68 minutes and increased with the number of implanted clips. Median total length of stay was 8 days. The occurrence of a serious adverse event was not associated with an increased risk of admission to the critical care unit, but was associated with an increased length of stay. The mean total cost was 28,025±3424€, which includes 21,547€ for the cost of medical devices used during pMVR and 6478±3424€ for other costs. CONCLUSION: The cost of pMVR is substantial for patients with SMR, which advocates for further efforts to identify the patients with SMR who are likely to derive a clear clinical benefit from the procedure.

Dismal Outcomes and High Societal Burden of Mitral Valve Regurgitation in France in the Recent Era: A Nationwide Perspective.

Background Although US recent data suggest that mitral regurgitation (MR) is severely undertreated and carries a poor outcome, population-based views on outcome and management are limited. We aimed to define the current treatment standards, clinical outcomes, and costs related to MR at the nationwide level. Methods and Results In total, 107 412 patients with MR were admitted in France in 2014 to 2015. Within 1 year, 8% were operated and 92% were conservatively managed and constituted our study population (68% primary MR and 32% secondary MR). The mean age was 77±15 years; most patients presented with comorbidities. In-hospital and 1-year mortality rates were 4.1% and 14.3%, respectively. Readmissions were common (63% at least once and 37% readmitted ≥2 times). Rates of 1-year mortality or all-cause readmission and 1-year mortality or heart failure readmission were 67% and 34%, respectively, and increased with age, Charlson index, heart failure at admission, and secondary MR etiology; however, the event rate remained notably high in the primary MR subset (64% and 28%, respectively). The mean costs of hospital admissions and of readmissions were 5345±6432 and 10 080±10 847 euros, respectively. Conclusions At the nationwide level, MR was a common reason for admission and affected an elderly population with frequent comorbidities. Less than 10% of patients underwent a valve intervention. All subsets of patients who were conservatively managed incurred high mortality and readmissions rates, and MR represented a major societal burden with an extrapolated annual cost of 350 to 550 million euros (390-615 million US dollars). New strategies to improve the management and outcomes of patients with both primary and secondary MR are critical and warranted.

Educational needs among physicians treating patients with atrial fibrillation: lessons for Poland from the European Society of Cardiology international educational needs assessment study.

INTRODUCTION: A study by the European Society of Cardiology assessing international educational needs has identified educational and organizational barriers preventing the implementation of optimal therapy of atrial fibrillation (AF) across European countries. OBJECTIVES: Our aim was to investigate educational and organizational barriers in the implementation of guideline­recommended AF care that are specific to physicians and health-care system in Poland. PATIENTS AND METHODS: An internet­based survey was conducted to assess education, skills, and confidence in managing patients with AF among European cardiologists, neurologists, and family physicians (FPs) from 6 countries. RESULTS: Out of 571 respondents, the Polish sample included 90 physicians (16%): 44 cardiologists (15%), 21 neurologists (16%), and 25 FPs (18%). Polish physicians generally reported skills and confidence similar to those presented by their foreign colleagues, but there was high uncertainty concerning skills and confidence in the identification and pathophysiological classification of AF. Also, FPs reported low confidence in applying CHA2DS2­VASc and HAS­BLED scores to clinical practice. The need for access to long­term heart rhythm monitoring including implantable loop recorders was highlighted. There was a general dissatisfaction with the cooperation among Polish physicians, which was significantly higher than in other countries. CONCLUSIONS: The number of substantial educational gaps among physicians from Poland and other European countries is low. Nonetheless, educational programs tailored for different specialist groups separately to improve competence are warranted. There is a clear need for improvement of communication among different specialists treating patients with AF in Poland.

Major knowledge gaps and system barriers to guideline implementation among European physicians treating patients with atrial fibrillation: a European Society of Cardiology international educational needs assessment.

Aims: Guideline-adherent treatment is associated with improved prognosis in atrial fibrillation (AF) patients but is insufficiently implemented in clinical practice. The European Society of Cardiology (ESC) performed a multinational educational needs assessment study among cardiologists, general practitioners/family physicians (GPs/FPs), and neurologists in order to evaluate knowledge and skills of physicians and system factors related to AF care delivery. Methods and results: A total of 561 physicians (294 cardiologists, 131 neurologists, and 136 GPs/FPs) from six European countries participated. This mixed-methods study included exploratory semi-structured qualitative interviews (n = 30) and a quantitative survey that included two clinical cases (n = 531). We identified eight key knowledge gaps and system barriers across all domains of AF care. A majority across all specialties reported skills needing improvement to classify AF pathophysiologically, rather than based on duration of episodes, and reported lack of availability of long-term electrocardiogram recording. Skills interpreting the CHA2DS2-VASc and the HAS-BLED scores were reported as needing improvement by the majority of neurologists (52% and 60%, respectively) and GPs/FPs (65% and 74%). Cardiologists calculated the CHA2DS2-VASc and HAS-BLED scores in 94%/70% in a presented case patient, but only 60%/49% of neurologists and 58%/42% of GPs/FPs did. There was much uncertainty on how to deal with anticoagulant therapy in complex patients. There was also a high disparity in using rate or rhythm control strategies, and indications for ablation. Information delivery to patients and communication between different specialties was often considered suboptimal, while national regulations and restrictions often hamper international guideline implementation. Conclusion: We identified major gaps in physicians' knowledge and skills across all domains of AF care, as well as system factors hampering guideline-compliant care implementation and communication. These gaps should be addressed by targeted educational and advocacy efforts.

Transcatheter Replacement of Failed Bioprosthetic Valves: Large Multicenter Assessment of the Effect of Implantation Depth on Hemodynamics After Aortic Valve-in-Valve.

BACKGROUND: Transcatheter valve implantation inside failed bioprosthetic surgical valves (valve-in-valve [ViV]) may offer an advantage over reoperation. Supra-annular transcatheter valve position may be advantageous in achieving better hemodynamics after ViV. Our objective was to define targets for implantation that would improve hemodynamics after ViV. METHODS AND RESULTS: Cases from the Valve-in-Valve International Data (VIVID) registry were analyzed using centralized core laboratory assessment blinded to clinical events. Multivariate analysis was performed to identify independent predictors of elevated postprocedural gradients (mean ≥20 mm Hg). Optimal implantation depths were defined by receiver operating characteristic curve. A total of 292 consecutive patients (age, 78.9±8.7 years; 60.3% male; 157 CoreValve Evolut and 135 Sapien XT) were evaluated. High implantation was associated with significantly lower rates of elevated gradients in comparison with low implantation (CoreValve Evolut, 15% versus 34.2%; P=0.03 and Sapien XT, 18.5% versus 43.5%; P=0.03, respectively). Optimal implantation depths were defined: CoreValve Evolut, 0 to 5 mm; Sapien XT, 0 to 2 mm (0-10% frame height); sensitivities, 91.3% and 88.5%, respectively. The strongest independent correlate for elevated gradients after ViV was device position (high: odds ratio, 0.22; confidence interval, 0.1-0.52; P=0.001), in addition to type of device used (CoreValve Evolut: odds ratio, 0.5; confidence interval, 0.28-0.88; P=0.02) and surgical valve mechanism of failure (stenosis/mixed baseline failure: odds ratio, 3.12; confidence interval, 1.51-6.45; P=0.002). CONCLUSIONS: High implantation inside failed bioprosthetic valves is a strong independent correlate of lower postprocedural gradients in both self- and balloon-expandable transcatheter valves. These clinical evaluations support specific implantation targets to optimize hemodynamics after ViV.

Multiple valve disease - assessment, strategy and intervention.

Patients with multiple valve disease are a frequent and heterogeneous entity whose evaluation and management are challenging. The assessment of the severity requires a cautious integrative evaluation. The indications for intervention are based on global assessment of the consequences of the disease, mainly based on symptoms, pulmonary hypertension, and left ventricular dysfunction. The decision to intervene should also take into account the inherent additional risk. Percutaneous intervention in this population is in its infancy but the future development of transcatheter techniques will be of interest in this high-risk cohort and will offer the possibility of tailored and staged procedures.

Comparative assessment of ascending aortic aneurysms in Marfan patients using ECG-gated computerized tomographic angiography versus trans-thoracic echocardiography.

BACKGROUND: Contrast-enhanced computed tomography (CT) is routinely used as a complementary technique to trans-thoracic echocardiography (TTE) for assessing thoracic aortic aneurysms (TAA). However different measures can be obtained on CT and there are no recommendations on which to use. The objective was to determine which CT measurements most closely match reference TTE measurements in Marfan patients with TAA. METHODS: TTE measurements were obtained using the leading edge-to-leading edge technique in end-diastole on the parasternal longitudinal view. ECG-gated CT measurements were obtained, using the inner-to-inner technique in end-diastole by double oblique reconstruction: on three-cavity view (3C), left ventricle-aorta view (LVAo), and strict transverse plane passing through the maximal diameter "cusp to commissure" and "cusp to cusp" for each cusp. CT and TTE were performed within one month. RESULTS: 44 Marfan patients (39 ± 19 years, 48% men) were included. Dilatation of the ascending aorta was maximal at the level of the sinuses (TTE diameters: mean 47.5 ± 5.3 mm). TTE diameters were similar to 3C, LVAo (mean differences: 2.2 and -0.1 mm, p=NS) and to the three "cusp to cusp" diameters (mean differences ranging from 0 to 1.1mm, p=NS), whereas "cusp to commissure" diameters were all statistically smaller than TTE (3.6 mm, 2.9 mm and 3.7 mm, p ≤ 0.01). CONCLUSIONS: Inner-to-inner "cusp to cusp" diameter measured on an ECG-gated CT should be used for comparison with 2D TTE aortic diameter at the level of the sinuses of Valsalva in patients with thoracic aortic aneurysms.

Predictive factors of early mortality after transcatheter aortic valve implantation: individual risk assessment using a simple score.

OBJECTIVE: Decision making for intervention in symptomatic aortic stenosis should balance the risks of surgery and of transcatheter aortic valve implantation (TAVI). We identified the factors associated with early mortality after TAVI and aimed to develop and validate a simple risk score. METHODS: A population of 3833 consecutive patients was randomly split into two cohorts comprising 2552 and 1281 patients, used respectively to develop and validate a scoring system predicting 30-day or in-hospital mortality. RESULTS: TAVI was performed using the Edwards Sapien prosthesis in 2551 (66.8%) patients and the Medtronic Corevalve in 1270 (33.2%). Approach was transfemoral in 2801 (73.4%) patients, transapical in 678 (17.8%), subclavian in 219 (5.7%) and other in 117 (3.1%). Early mortality was 10.0% (382 patients). A multivariate logistic model identified the following predictive factors of early mortality: age ≥90 years, body mass index <30 Kg/m(2), New York Heart Association class IV, pulmonary hypertension, critical haemodynamic state, ≥2 pulmonary oedemas during the last year, respiratory insufficiency, dialysis and transapical or other (transaortic and transcarotid) approaches. A 21-point predictive score was derived. C-index was 0.67 for the score in the development cohort and 0.59 in the validation cohort. There was a good concordance between predicted and observed 30-day mortality rates in the development and validation cohorts. CONCLUSIONS: Early mortality after TAVI is mainly related to age, the severity of symptoms, comorbidities and transapical approach. A simple score can be used to predict early mortality after TAVI. The moderate discrimination is however a limitation for the accurate identification of high-risk patients.

Comparison of semiquantitative and quantitative assessment of severity of aortic regurgitation: clinical implications.

BACKGROUND: Recent studies have emphasized the importance of quantitative assessment of the degree of aortic regurgitation (AR). However, semiquantitative methods have remained mainly used despite their unclear diagnostic value. The aim of this study was to define the sensitivity and specificity of semiquantitative methods compared with the proximal isovelocity surface area method as a reference for the diagnostic of severe AR. METHODS: The degree of AR was evaluated using the proximal isovelocity surface area method and four semiquantitative measurements (left ventricular cardiac output, pressure half-time, diastolic flow reversal, and vena contracta) in 224 patients with a wide range of AR severity. RESULTS: The mean effective regurgitant orifice area was 25 ± 14 mm(2) (range, 3-69 mm(2)), the mean regurgitant volume was 57 ± 31 mL (range, 9-183 mL), and 100 patients (44%) had severe AR (effective regurgitant orifice area ≥ 30 mm(2) or regurgitant volume ≥ 60 mL). Overall, semiquantitative methods had good specificity but poor sensitivity, except the vena contracta, which had good sensitivity and specificity. Sensitivity, specificity, and positive and negative predictive values of the recommended thresholds for severe AR of the four semiquantitative methods were 53%, 89%, 77%, and 73% for left ventricular cardiac output ≥ 10 L/min; 12%, 100%, 100%, and 52% for pressure half-time < 200 msec; 45%, 87%, 79%, and 60% for diastolic flow reversal ≥ 18 cm/sec; and 81%, 83%, 78%, and 85% for vena contracta ≥ 6 mm, respectively. CONCLUSIONS: For the assessment of AR severity, current thresholds appear specific but poorly sensitive, except for vena contracta, which provides good discriminative value. Semiquantitative methods should be integrated into the comprehensive evaluation of AR severity, but severe AR should not be excluded only on the basis of semiquantitative criteria. These results emphasize the need for the quantitative assessment of AR severity.

Echocardiographic right ventricular function assessment before and after successful percutaneous mitral commissurotomy.

BACKGROUND AND AIM OF THE STUDY: In patients with mitral stenosis (MS), previous studies have shown discordant results with regards to improvements in right ventricular (RV) function immediately after percutaneous mitral commissurotomy (PMC). Hence, the study aim was to evaluate the impact of PMC on RV function, by using Doppler-echocardiography. METHODS: A total of 41 patients with severe symptomatic MS, in sinus rhythm, who had been referred to the authors' institution for PMC, was prospectively enrolled. A group of 25 healthy age- and gender-matched subjects served as controls. Transthoracic echocardiography (TTE) was performed on the day before and at 24/48 h after PMC. The RV function was evaluated using the Tricuspid Annular Plane Excursion (TAPSE), the RV Tei index, and systolic myocardial velocities by Doppler tissue imaging peak isovolumic contraction (DTI(IVC)) and peak systolic (DTI(S)) at the lateral tricuspid annulus). RESULTS: All patients but three underwent a successful PMC. The mitral valve area (MVA) was significantly increased (1.8 +/- 0.3 versus 1.1 +/- 0.2 cm2, p <0.0001), while the mean gradient (5 +/- 2 versus 10 +/- 7 mmHg, p <0.0001) and systolic pulmonary artery pressure (40 +/- 10 versus 54 +/- 21 mmHg, p = 0.0002) were decreased. Compared to healthy controls, the RV dysfunction in MS patients was authenticated by the DTI(IVC) and the Tei index (8.4 +/- 3.0 versus 11.1 +/- 2.1 cm/s, p = 0.0002 and 0.33 +/- 0.10 versus 0.18 +/- 0.10 respectively, p <0.0001), but not by DTI(S) (12.9 +/- 3 versus 12.3 +/- 1.5 cm/s, p = 0.35) or TAPSE (24 +/- 5 versus 23 +/- 3 mm, p = 0.50). After PMC, no significant change regarding RV function was observed (TAPSE: 24 +/- 5 versus 24 +/- 5 mm, p = 0.54; Tei Index: 0.33 +/- 0.10 versus 0.36 +/- 0.12, p = 0.20; DTI(IVC): 8.4 +/- 3.0 versus 9.2 +/- 3.4 cm/s, p = 0.08 and DTI(S): 12.9 +/- 3.0 versus 13.0 +/- 3.4 cm/s, p = 0.54). CONCLUSION: The DTI(IVC) and Tei index appear to serve as the more sensitive indices of RV dysfunction in patients with MS. Immediately after a successful PMC, no significant change in Doppler echocardiographic parameters of RV function was observed. Whether late improvement in RV function can be observed, and the prognostic value of these parameters realized, deserve further investigation.

Multimodal assessment of the aortic annulus diameter: implications for transcatheter aortic valve implantation.

OBJECTIVES: We sought to compare 3 methods of measurements of the aortic annulus, transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and multislice computed tomography (MSCT), and to evaluate their potential clinical impact on transcatheter aortic valve implantation (TAVI) strategy. BACKGROUND: Exact measurement of the aortic annulus is critical for a patient's selection and successful implantation. METHODS: Annulus diameter was measured using TTE, TEE, and MSCT in 45 consecutive patients with severe aortic stenosis referred for TAVI. The TAVI strategy (decision to implant and choice of the prosthesis' size) was based on manufacturer's recommendations (Edwards-Sapien prosthesis, Edwards Lifesciences, Inc., Irvine, California). RESULTS: Correlations between methods were good but the difference between MSCT and TTE (1.22 +/- 1.3 mm) or TEE (1.52 +/- 1.1 mm) was larger than the difference between TTE and TEE (0.6 +/- 0.8 mm; p = 0.03 and p < 0.0001, respectively). Regarding TAVI strategy, agreement between TTE and TEE overall was good (kappa = 0.68), but TAVI strategy would have been different in 8 patients (17%). Agreement between MSCT and TTE or TEE was only modest (kappa = 0.28 and 0.27), and a decision based on MSCT measurements would have modified the TAVI strategy in a large number of patients (40% to 42%). Implantation, performed in 34 patients (76%) based on TEE measurements, was successful in all but 1 patient with grade 3/4 regurgitation. CONCLUSIONS: In patients referred for TAVI, measurements of the aortic annulus using TTE, TEE, and MSCT were close but not identical, and the method used has important potential clinical implications on TAVI strategy. In the absence of a gold standard, a strategy based on TEE measurements provided good clinical results.

Understanding risk assessment in cardiac surgery patients.

Understanding the risk of surgery in valvular disease is of interest because aging of the population renders decision making more difficult and the magnitude of risk will influence not only the decision to intervene but also the choice of intervention and its timing. To assist clinicians in assessing the risk of cardiac surgery, multivariate risk scores are increasingly used to estimate operative mortality. Overall, the currently available scores, mostly U.S. Society of Thoracic Surgeons score and European System for Cardiac operative Risk Evaluation, achieve acceptable discrimination but suboptimal calibration in estimating the operative mortality of heart valve surgery. The intrinsic limitations of scoring systems highlight the fact that risk scores should be integrated into clinical judgment but should not be a substitute for it. A multidisciplinary approach involving cardiologists, cardiac surgeons, and anesthesiologists is required for this purpose, especially in high-risk patients.

Results of transfemoral or transapical aortic valve implantation following a uniform assessment in high-risk patients with aortic stenosis.

OBJECTIVES: We sought to describe the results of a strategy offering either transfemoral or transapical aortic valve implantation in high-risk patients with severe aortic stenosis. BACKGROUND: Results of transfemoral and transapical approaches have been reported separately, but rarely following a uniform assessment to select the procedure. METHODS: Of 160 consecutive patients at high risk or with contraindications to surgery, referred between October 2006 and November 2008, 75 were treated with transcatheter aortic valve implantation. The transfemoral approach was used as the first option and the transapical approach was chosen when contraindications to the former were present. The valve used was the Edwards Lifesciences SAPIEN prosthesis. RESULTS: Patients were age 82 +/- 8 years (mean +/- SD), in New York Heart Association functional classes III/IV, with predicted mean surgical mortalities of 26 +/- 13% using the European System for Cardiac Operative Risk Evaluation and 16 +/- 7% using the Society of Thoracic Surgeons Predicted Risk of Mortality. Fifty-one patients were treated via the transfemoral approach, and 24 via the transapical approach. The valve was implanted in 93% of the patients. Hospital mortality was 10%. Mean (+/- SD) 1-year survivals were 78 +/- 6% in the whole cohort, 81 +/- 7% in the transfemoral group, 74 +/- 9% in the transapical group (p = 0.22), and 60 +/- 10% in the first 25 patients versus 93 +/- 4% in the last 50 patients treated (p = 0.001). In multivariate analysis, early experience was the only significant predictor of late mortality. CONCLUSIONS: Being able to offer either transfemoral or transapical aortic valve implantation, within a uniform assessment, expands the scope of the treatment of aortic stenosis in high-risk patients and provides satisfactory results at 1 year in this population. The results are strongly influenced by experience.

Age, outcomes, and treatment effects of fibrinolytic and antithrombotic combinations: findings from Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-3 and ASSENT-3 PLUS.

BACKGROUND: Elderly patients with acute myocardial infarction are at particularly high risk for death and bleeding complications. The efficacy and safety of antithrombotic strategies in these patients remain unclear. METHODS: To provide more insight into the risk and benefit of antithrombotic strategies in the elderly, we examined patients from the ASSENT-3 and ASSENT-3 PLUS trials with STEMI who were treated with tenecteplase (TNK) and unfractionated heparin (UFH) or enoxaparin, or half-dose TNK with abciximab and reduced-dose UFH. RESULTS: Older patients had a higher risk profile, and lower use of concomitant therapies and revascularization procedures. We found an interaction between age and treatment effect for the efficacy end point (P = .0007) and the efficacy plus safety end point (P < .0001). Younger patients (<65 years) had a lower risk of the composite efficacy plus safety end point with enoxaparin (relative risk [RR] 0.84, 95% CI 0.74-0.94) or abciximab (RR 0.79, 95% CI 0.69-0.90) compared with UFH. In patients >65 years of age, the benefit of enoxaparin appeared to be offset by an increased risk of bleeding complications. The risk of the efficacy plus safety end point tended to be higher in elderly patients receiving abciximab and half-dose TNK (RR 1.18, 95% CI 0.91-1.51 for 76-85 years of age and RR 1.48, 95% CI 0.88-2.49 for >85 years of age). CONCLUSIONS: Although TNK with either enoxaparin or abciximab appeared to be more effective than with standard UHF in younger patients, these combinations tended to be less effective and even may be unsafe in the elderly. Development of new combination strategies and dosing schemes of fibrinolytics and antithrombotics with improved efficacy and safety in the elderly remains a high priority.