Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Dyspnea on exertion is an independent predictor of mortality in patients with no baseline cardiovascular or respiratory disorders

Abstract Background Dyspnea on exertion (DOE) is defined as a subjective experience of breathing discomfort that consists of qualitatively distinct sensations (Effort/work of breathing, Chest tightness, Air hunger) that vary in intensity elicited by physical activity. Although DOE is a common presenting symptom in patients pertaining to cardiovascular and respiratory disorders, its prognostic importance in patients with no prior cardiovascular (CV) or respiratory disorders is unclear. Purpose The purpose of this study is to determine the prognostic significance of dyspnea on exertion (DOE) in patients with no prior diagnosis of CV or respiratory disorders. Methods We reviewed the Mayo Integrated Stress Center database for the period September 1993 through November 2010. Residents of Minnesota with no known heart disorders and no known history of COPD or other respiratory disorders were included in the study. Patients with abnormal ECG findings were excluded to rule out possible undiagnosed CV disorders. Limiting symptoms of DOE with reduced exercise capacity (FAC&amp;lt;90%). Our primary outcome was mortality which was adjusted for age, sex, smoking history, diabetes, hypertension, obesity, negative chronotropic medications. Statistical analysis was performed to evaluate hazard ratio using Cox regression models in SAS Studio. Results A total of 101,455 exercise tests were reviewed to identify 18960 patients (female = 6755, 35.6%) who met the study criteria. Mean age at the time of referral was 51.2±10 years (mean ± SD) and mean follow-up was 12±10 years (mean ± SD). There were 1331 (7%) deaths from all causes, out of which 368 (27.6%) deaths are from DOE patients, and there were 428 (2.2%) deaths from cardiac causes, out of which 141 (32.9%) deaths are from DOE patients. We found that DOE was an independent predictor of mortality from all causes with hazard ratio [95% CI] = 1.690 [1.488–1.918], p≤0.0001, and from cardiac causes with hazard ratio [95% CI] = 1.997 [1.613–2.473], p≤0.0001. Product-limit survival estimates of patients with and without DOE are shown in Figure 1. Conclusion Based on our study findings, we conclude that dyspnea on exertion is an independent predictor of mortality in patients with no baseline CV or respiratory disorders. Patients presenting with dyspnea alone as a presenting compliant should be evaluated thoroughly and treated accordingly to reduce the associated mortality outcomes. Figure 1. Kaplan-Meier Plot Funding Acknowledgement Type of funding source: None </jats:sec

P3105Cardiopulmonary exercise testing normal values for young athletes and non-athletes

Abstract Introduction Cardiopulmonary exercise testing (CPET) is an important diagnostic method to evaluate athletes and non-athletes, however we do not have widely accepted normal values for correct evaluation and interpretation in the young. Goals Our aim was to compare CPET parameters of young athletes and non-athletes and determine reference values. Methods Exercise tests were performed in young non-athletes, aged &lt;18 years between 2011 to 2016 at Mayo Clinic. Athletes underwent detailed sports cardiology screening including CPET at Semmelweis University Heart and Vascular Center between 2016 and 2018. Individuals with cardiovascular disease were excluded. We created 2 subgroups in both sexes: 12–14 years (Group 1), 15–17 years (Group 2). Statistical analysis was performed using SAS with analysis of variance under the general linear model adjusting for age, body mass index and test effort based on peak respiratory exchange ratio (RER). Results A total of 212 athletes (92% male, 15.5±0.6ys) and 207 non-athletes (68% male, 15.0±0.7ys) were included in the analysis. In Group 1 boys, athletes have higher peak HR (200.0±9.2 vs 188.5±16.8 bpm, p&lt;0.0001), HR reserve (117.1±14.5 vs 108.9±19.8 bpm p&lt;0.05), VO2 max (53.7±6.6 vs 44.7±9.1 mL/kg/min p&lt;0.0001), ventilation (VE) (120.3±25.0 vs 70.7±21.6 L/min p&lt;0.0001) and RER (1.12±0.0 vs 1.07±0.08, p &lt;.001) compared to controls. In Group 2 boys, there was no difference in peak HR and HR reserve, but athletes have higher VO2 max (57.2±4.7 vs 45.3±9.3 mL/kg/min, p&lt;0.0001) and VE (150.7±23.7 vs 104.1±25.9 L/min, p&lt;0.0001), similarly as Group 2 girls: VO2 max (46.3±3.6 vs 34.9±8.5 mL/kg/min p&lt;0.0001), VE (118.7±12.5 vs 68.4±20.6 L/min, p&lt;0.0001). In male athletes, peak HR (200.6±9.2 vs 196.5±7.4 bpm p&lt;0.05) and HR recovery (34.2±9.8 vs 29.8±11.1 bpm p&lt;0.05) decreases with age, while VO2 max (53.7±6.6 vs 57.2±4.7 mL/kg/min, p&lt;0.001) and VE (120.3±24.9 vs 150.7±23.7 L/min, p&lt;0.0001) increases. Lower cut-off values were determined in each group (Figure). Lower-cut off values Conclusion We created a unique Mayo-Semmelweis database of young athletes and non-athletes. As a result of intensive training, athletes show higher levels of CPET variables vs non-athletes. Our study provides CPET reference values in the pediatric age group, applying them could contribute to correct evaluation and interpretation of CPET, increasing its diagnostic potential. </jats:sec