210Predictors of thromboembolism in patients with atrial fibrillation and valvular heart disease according to the EHRA classification: beyond mitral stenosis and mechanical prosthetic heart valves

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Melgaard ◽  
T F Overvad ◽  
M Jensen ◽  
P B Nielsen ◽  
G Y H Lip ◽  
...  

Abstract Background Atrial fibrillation (AF) and valvular heart disease (VHD) often coexist. They are independent causes of mortality and morbidity, and both have been associated with risk of thromboembolic events. Historically, the definition of VHD in AF patients has been inconsistent, which led to the proposal of a new classification of AF patients with VHD: the “Evaluated Heartvalves, Rheumatic or Artificial” (EHRA) valve classification, categorizing patients into: EHRA Type 1 VHD and EHRA Type 2 VHD. EHRA Type 1 VHD comprises AF patients with mitral stenosis (moderate-severe, of rheumatic origin) or a mechanical prosthetic valve replacement. EHRA Type 2 VHD includes AF patients with any other heart valve disease or a bioprosthetic valve replacement. The thromboembolic risk in this latter heterogeneous group is uncertain and, thus, identifying clinically relevant predictors of thromboembolism will facilitate more individualized risk stratification and identify high-risk subgroups, thereby, optimize prevention strategies. Purpose In a large nationwide cohort study, we aimed to identify clinically relevant predictors of thromboembolism in AF patients with EHRA Type 2 VHD. Methods We conducted a cohort study of AF patients with co-existing EHRA Type 2 VHD, identified by ICD-10 codes using record linkage between nationwide registries in Denmark from 2000 through 2018. Time-to-event analysis was applied to describe the association between EHRA Type 2 VHD and risk of thromboembolism. We used a multivariable Cox proportional hazards regression model with time since incident AF diagnosis as the underlying time axis to estimate predictors of the outcome at 5-years of follow-up. Parameters included were clinically relevant risk factors, statin therapy, antithrombotic therapy, and time since VHD diagnosis. Results A total of 27,254 patients with EHRA Type 2 VHD was identified. After 5 years of follow-up, the rate of thromboembolism was 3.27 per 100 person-years. History of thromboembolism (HR: 4.85, 95% CI: 4.43–5.31) and age ≥75 (HR: 1.97, 95% CI: 1.70–2.28) were the strongest predictors of thromboembolism, but age 65–74, female sex, vascular disease, diabetes mellitus, hyperlipidemia/hypercholesterolemia, history of bleeding, and increasing CHA2DS2-VASc score were also independent predictors [Figure]. Predictors of thromboembolism Conclusion Among AF patients with VHD beyond mitral stenosis and mechanical prosthetic heart valves, the rate of thromboembolism is high after 5 years of follow-up. The strongest clinically relevant predictors of thromboembolism are history of thromboembolism and age ≥75. Future studies examining the optimal antithrombotic prevention strategy for EHRA Type 2 VHD are encouraged. Acknowledgement/Funding The study was supported by “The BMS/Pfizer European Thrombosis Investigator Initiated Research Program 2018 (ERISTA)” and the Obel Family Foundation.

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
L Fauchier ◽  
A Bisson ◽  
G Fauchier ◽  
A Bodin ◽  
J Herbert ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background. There remain uncertainties regarding diabetes mellitus and the incidence of atrial fibrillation (AF), in relation to type of diabetes, and the interactions with sex and age. We investigated whether diabetes confers higher relative rates of AF in women compared to men, and whether these sex-differences depend on type of diabetes and age. Methods. All patients aged > =18 seen in French hospitals in 2013 with at least 5 years of follow-up without a history of AF were identified and categorized by their diabetes status. We calculated overall and age-dependent incidence rates, hazard ratios, and women-to-men ratios for incidence of AF in patients with type 1 and type 2 diabetes (compared to no diabetes). Results. In 2,921,407 patients with no history of AF (55% women), 45,389 had prevalent type 1 diabetes and 345,499 had prevalent type 2 diabetes. During 13.5 million person-years of follow-up, 327,012 patients with new-onset AF were identified. The incidence rates (IRs) of AF were higher in type 1 or type 2 diabetic patients than in non-diabetics, and increased with advancing age. Among individuals with diabetes, the absolute rate of AF was higher in men than in women. When comparing individuals with and without diabetes, women had a higher adjusted hazard ratio (HR) of AF than men: adjusted HR 1.32 (95% confidence interval 1.27-1.37) in women vs. 1.12(1.08-1.16) in men for type 1 diabetes, adjusted HR 1.17(1.16-1.19) in women vs. 1.10(1.09-1.12) in men for type 2 diabetes.  The adjusted HRs for women were significantly higher than the adjusted HRs for men as shown with the adjusted women-to-men ratios (adjusted WMR = adjusted HR women compared to adjusted HR men) = 1.18 (95%CI 1.12-1.24) for type 1 diabetes and 1.10 (95%CI 1.08-1.12) for type 2 diabetes. This phenomenon was seen across all ages in men and women with type 1 diabetes and progressively decreased with advancing age.  In type 2 diabetes, this phenomenon was seen after 50 years, increased until 60-65 years and then progressively decreased with advancing age. Conclusion. Although men have higher absolute rates for incidence of AF, the relative rates of incident AF associated with diabetes are higher in women than in men for both type 1 and type 2 diabetes.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Lu Liu ◽  
Xiaoling Guan ◽  
Zhongshang Yuan ◽  
Meng Zhao ◽  
Qiu Li ◽  
...  

Aim. It is known that different stages of type 2 diabetes represent distinct pathophysiological changes, but how the spectrum of risk factors varies at different stages is not yet clarified. Hence, the aim of this study was to compare the effect of different metabolic variables on the natural history of type 2 diabetes. Methods. A total of 5,213 nondiabetic (normal glucose tolerance (NGT) and prediabetes) Chinese older than 40 years participated this prospective cohort study, and 4,577 completed the 3-year follow-up. Glycemic status was determined by standard oral glucose tolerance test both at enrollment and follow-up visit. Predictors for conversion in glycemic status were studied in a corresponding subcohort using the multiple logistic regression analysis. Results. The incidence of prediabetes and diabetes of the cohort was 93.6 and 42.2 per 1,000 person-years, respectively. After a 3-year follow-up, 33.1% of prediabetes patients regressed to NGT. The predictive weight of body mass index (BMI), serum triglyceride, total cholesterol, and systolic blood pressure in different paths of conversions among diabetes, prediabetes, and NGT differed. Specifically, BMI was the strongest predictor for regression from prediabetes to NGT, while triglyceride was most prominent for onset of diabetes. One SD increase in serum triglyceride was associated with a 1.29- (95% CI 1.10–1.52; P=0.002) or 1.12- (95% CI 1.01–1.27; P=0.039) fold higher risk of diabetes for individuals with NGT or prediabetes, respectively. Conclusion. Risk factors for different stages of diabetes differed, suggesting personalized preventive strategies for individuals with different basal glycemic statuses.


BMJ Open ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. e033712
Author(s):  
José Miguel Rivera-Caravaca ◽  
Francisco Marín ◽  
María Asunción Esteve-Pastor ◽  
Josefa Gálvez ◽  
Gregory Y.H. Lip ◽  
...  

IntroductionAtrial fibrillation (AF) is characterised by a high stroke risk. Vitamin K antagonists (VKAs) are the most commonly used oral anticoagulants (OACs) in Spain, but their efficacy and safety depend on the time in therapeutic range of International Normalized Ratio (INR) 2.0–3.0 over 65%–70%. Unfortunately, the difficulties of maintaining an optimal level of anticoagulation and the complications of VKAs (particularly haemorrhagic ones), frequently lead to cessation of this therapy, which has been associated with higher risk of adverse events (AEs), including ischaemic stroke. Our aims are as follows: (1) to evaluate the quality of oral anticoagulation with VKAs, the prevalence of poor quality of anticoagulation, and to identify factors predisposing to poor quality anticoagulation; and (2) to identify patients who will stop OAC and to investigate what factors influence the decision of OAC withdrawal.Methods and analysisProspective observational cohort study including outpatients newly diagnosed with AF and naïve for OACs from July 2016 to June 2018 in an anticoagulation clinic. Patients with prosthetic heart valves, rheumatic mitral valves or valvular AF will be excluded. Follow-up will extend for up to 3 years. During this period, the INR results and changes in the anticoagulant therapy will be recorded, as well as all AEs, or any other information that would be relevant to the proper conduct of research.Ethics and disseminationAll patients were informed about the nature and purpose of the study, and the protocol was approved by the Ethics Committee of Hospital General Universitario Morales Meseguer (reference: EST:20/16). This is an observational study focusing on ‘real life’ practice and therefore all treatments and follow-up will be performed in accordance to the routine clinical practice with no specific interventions or visits. The results of our study will be disseminated by presentations at national and international meetings, and publications in peer-reviewed journals.


EP Europace ◽  
1999 ◽  
Vol 1 (1) ◽  
pp. 35-39 ◽  
Author(s):  
L. Gianfranchi ◽  
M. Brignole ◽  
C. Menozzi ◽  
G. Lolli ◽  
N. Bottoni

Abstract We evaluated the rate of progression of permanent atrial fibrillation (AF) and identified clinical factors that predict this event in 63 consecutive patients who had undergone AV junctional ablation and DDDR pacemaker implantation for drug-refractory paroxysmal atrial fibrillation/flutter. Immediately after ablation, anti-arrhythmic drugs were discontinued in all cases. Permanent AF was con-sidered to have developed if AF was present on two consecutive 6-monthly examinations with no interim documented sinus rhythm. During a mean follow-up of 23±16 months, 22 (35%) of the 63 patients developed permanent AF. The actuarial estimate of progression of permanent AF was 22%, 40% and 56%, respectively, 1, 2 and 3 years after ablation. Age and underlying heart disease were independent predictors of progression of permanent AF. Only one (6%) of 16 patients with idiopathic AF had permanent AF (low risk group). Among the 47 patients with structural heart disease, permanent AF developed in 18 (62%) of the 29 who were aged >75 years or had >12 arrhythmic episodes per year and a symptom duration >4 years (high risk group), but only in three (17%) of the remaining 18 patients who did not (intermediate risk group). In conclusion, during a 3-year follow-up period, about half of the patients with a history of drug-refractory paroxysmal AF did not develop permanent AF after AV junctional ablation and dual-chamber pacemaker implantation, even in the absence of anti-arrhythmic drug therapy. Moreover, subgroups of patients whose risk of permanent AF progression differed were identified on the basis of simple baseline clinical variables. The results of this study form the necessary background for the correct management of patients after AV junction ablation and for the planning of future trials in this field.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Polovina ◽  
I Milinkovic ◽  
G Krljanac ◽  
I Veljic ◽  
I Petrovic-Djordjevic ◽  
...  

Abstract Background Type 2 diabetes (T2DM) portends adverse prognosis in patients with atrial fibrillation (AF). Whether T2DM independently increases the risk of incident heart failure (HF) in AF is uncertain. Also, HF phenotype developing in patients with vs. those without T2DM has not been characterised. Purpose In AF patients without a history of prior HF, we aimed to assess: 1) the impact of T2DM on the risk of new-onset HF; and 2) the association between T2DM and HF phenotype developing during the prospective follow-up. Methods We included diabetic and non-diabetic AF patients, without a history of HF. Baseline T2DM status was inferred from medical history, haemoglobin A1c levels and oral glucose tolerance test. Study outcome was the first hospital admission or emergency department treatment for new-onset HF during the prospective follow-up. The phenotype of new-onset HF was determined by echocardiographic exam performed following clinical stabilisation (at hospital discharge, or within a month after HF diagnosis). HF phenotype was defined as HFrEF (left ventricular ejection fraction [LVEF] <40%), HFmrEF (LVEF 40–49%) or HFpEF (LVEF≥50%). Cox regression analyses adjusted for age, sex, baseline LVEF, comorbidities, smoking status, alcohol intake, AF type (paroxysmal vs. non-paroxysmal) and T2DM treatment was used to analyse the association between T2DM and incident HF. Results Among 1,288 AF patients without prior HF (mean age: 62.1±12.7 years; 61% male), T2DM was present in 16.5%. Diabetic patients had higher mean baseline LVEF compared with nondiabetic patients (50.0±6.2% vs. 57.6±9.0%; P<0.001). During the median 5.5-year follow-up, new-onset HF occurred in 12.4% of patients (incidence rate, 2.9; 95% confidence interval [CI], 2.5–3.3 per 100 patient-years). Compared with non-diabetic patients, those with T2DM had a hazard ratio of 2.1 (95% CI, 1.6–2.8; P<0.001) for new-onset HF, independent of baseline LVEF or other factors. In addition, diabetic patients had a significantly greater decline in covariate-adjusted mean LVEF (−10.4%; 95% CI, −9.8% to −10.8%) at follow-up, compared with nondiabetic patients (−4.0%; 95% CI, −3.8% to −4.2%), P<0.001. The distribution of HF phenotypes at follow-up is presented in Figure. Among patients with T2DM, HFrEF (56.9%) was the most common phenotype of HF, whereas in patients without T2DM, HF mostly took the phenotype of HFpEF (75.0%). Conclusions T2DM is associated with an independent risk of new-onset HF in patients with AF and confers a greater decline in LVEF compared to individuals without T2DM. HFrEF was the most prevalent presenting phenotype of HF in AF patients with T2DM.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2950-2950 ◽  
Author(s):  
Tait D. Shanafelt ◽  
Kari G. Chaffee ◽  
Timothy G. Call ◽  
Sameer A. Parikh ◽  
Susan M. Schwager ◽  
...  

Abstract BACKGROUND: Consistent with the advanced age at diagnosis (median age ~70 years), most patients with CLL have co-existent health problems. These co-morbidities influence the ability of many CLL patients to tolerate aggressive chemotherapy-based treatment and can also contribute to treatment-related side effects. The recent development of novel signaling inhibitors, particularly the Bruton's tyrosine kinase inhibitor ibrutinib, has been a major treatment advance for patients with CLL. While these agents generally have favorable toxicity profiles relative to standard chemotherapy-based treatments, they are chronic therapies which patients typically stay on for an extended period. Preliminary data suggests ibrutinib may be associated with an increased risk of atrial fibrillation (Afib). In one randomized trial comparing ibrutinib to ofatumumab in patient with relapsed CLL, incident grade 3+ Afib occurred in 3% of ibrutinib treated patients compared to 0% of ofatumumab treated patients (NEJM 371:213). Despite these observations, the baseline frequency of Afib in patients with CLL is not well described - particularly incident atrial fibrillation acquired during the course of the disease. METHODS: We used the Mayo Clinic CLL database to evaluate the prevalence of Afib at the time of CLL diagnosis as well as the incidence of Afib during follow-up. All patients with a new diagnosis of CLL after January 1995 who were seen at Mayo within 12 months of diagnosis were included in the analysis. Afib was identified by chart review and by billing search using ICD9 codes. Data on co-morbid conditions associated with risk of Afib was also abstracted (e.g. hypertension, coronary artery disease [CAD], valvular heart disease, cardiomyopathy, diabetes mellitus, pulmonary disease). RESULTS: A total of 2444 patients with newly diagnosed and previously untreated CLL were seen at Mayo Clinic within 12 months of diagnosis between 1/1995 and 4/2015.Median age at diagnosis was 65 years and 1626 (66.5%) patients were men. A history of Afib was present at the time of CLL diagnosis in 148 (6.1%) patients. Four additional patients had Afib documented in the record but the precise date of onset (e.g. prior to or after CLL diagnosis date) could not be determined. Age, male sex and history of CAD, valvular heart disease, cardiomyopathy, hypertension, and diabetes were associated with a greater likelihood of having a history of Afib at the time of CLL diagnosis (all p&lt;0.01). Among the 2292 patients without a history of Afib at CLL diagnosis, 139 (6.1%) had incident Afib during the course of follow-up for their CLL. The incidence of Afib among patients without a history of Afib at diagnosis was approximately 1%/year (Figure 1A). Considering both Afib present at the time of CLL diagnosis or acquired during the course of the disease, 291 (11.9%) of the 2444 patients in this cohort experienced Afib (median follow-up: 59 months). Among patients without Afib at the time of CLL diagnosis, the following characteristics at the time of CLL diagnosis were associated with an increased risk of incident Afib on multivariate analysis: older age (age 65-74 HR=2.4, p&lt;0.001; age ≥75 HR=3.6, p&lt;0.001), male sex (HR=1.8, p=0.004); valvular heart disease (HR=2.4, p=0.007), and hypertension (HR=1.5; p=0.02). A predictive model for acquired Afib was subsequently constructed based on the independent factors in the Cox regression model. An individual weighted risk score was assigned to each independent factor based on the regression coefficients of the HRs. The Afib risk score (range 0-7) was defined as the sum of the scores of these independent factors. The risk of incident Afib among patients with risk scores of 0-1, 2-3, 4, and 5+ is shown in Figure 1B. Rates for these 4 groups were significantly different (p&lt;0.001), with the 10-year Afib rates (95% C.I.) for those with a score of 0-1, 2-3, 4, and 5+: 4% (2-6%), 9% (6-13%), 17% (11-23%), and 33% (20-43%), respectively. CONCLUSIONS: A history of Afib is present in approximately 1 out of every 16 patients with newly diagnosed CLL. Among patients without Afib at diagnosis, the incidence rate of Afib is ~1%/year. The risk of incident Afib in newly diagnosed CLL patients can be predicted based on age, sex, and co-morbid health conditions present at diagnosis. These data provide context to help interpret data on the frequency of Afib in CLL patients treated with ibrutinib and other novel agents. Disclosures Shanafelt: Janssen: Research Funding; Polyphenon E Int'l: Research Funding; Glaxo-Smith_Kline: Research Funding; Cephalon: Research Funding; Genentech: Research Funding; Hospira: Research Funding; Celgene: Research Funding; Pharmactckucs: Research Funding. Ding:Merek: Research Funding. Kay:Tolero Pharm: Research Funding; Hospira: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.


Author(s):  
S.M. Rajah ◽  
N. Sreeharan ◽  
S. Rao ◽  
D.A. Watson

The effect of Warfarin (W) was compared with a combination of Warfarin and Dipyridamole (W+D) on the incidence of arterial thrombo-embolism in patients with prosthetic heart valves in a prospective randomised study. Sixty-four and 53 patients were allocated to W and W+D. The two groups were comparable as regards age, sex, arrhythmias and site and type of valves. The dose of W was determined by regular monitoring of prothrombin ratio 0.9 - 3) and that of D by monitoring serum D levels to between 2 and 4 μmol/l. The mean period of follow-up was 26.98 months (range 1 to 36) for W and 22.02 months (range 1 to 36) for W+D. Six patients in W and 1 in W+D developed arterial thrombo-embolic episodes giving an incidence of 0.0035 per patient month for W and 0.0009 per patient month for W+D. An actuarial analysis of the yearly incidence of thrombo-embolism confirmed the superiority of W+D over W. Of the 6 failures in W, 5 were in sinus rhythm and 1 in atrial fibrillation and all had cerebral embolic episodes. The failure in W+D was a patient in atrial fibrillation who died suddenly 6 weeks after surgery and the post-mortem showed clots on both mitral and aortic prostheses.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Peter Leong-Sit ◽  
Karin H Humphries ◽  
May Lee ◽  
George J Klein ◽  
Robert Sheldon ◽  
...  

Background: The natural history of lone atrial fibrillation (AF) is unclear with conflicting data in the literature. We aimed to better describe the clinical outcomes and echocardiographic changes associated with lone AF. Methods: The Canadian Registry of Atrial Fibrillation (CARAF) enrolled 803 non-surgical and non-flutter patients with new onset AF between 1990 and 1996. At enrollment, patients were classified as lone AF (LAF) or not lone AF (Not LAF) based on structural heart disease or hyperthyroidism. Clinical data was prospectively collected with follow-up at 3 months, 1 year, then annually; echocardiograms were performed at enrollment and years 2, 4, and 7. Results: The LAF group (n=212) had a median age of 57 (1 st quartile 44, 3 rd quartile 67) while the Not LAF group (n=591) had a median age of 67 (59, 73), p<0.0001. During the median follow-up of 8 years in the LAF group and 7 years in the Not LAF group, there was a significant difference in survival free from stroke or embolism favoring the LAF group (Figure ). At 8 years, the probability of remaining free of chronic AF was 78.8% vs 69.3% (p=0.02) and free of symptomatic or documented recurrence of AF was 40.1% vs 26.9% (p<0.01) in the LAF vs Not LAF group. The LAF group had smaller LV diastolic and systolic dimensions by 5.5% and 10.2%, respectively, vs the Not LAF group (p<0.0001). The LV mass was smaller at baseline by 21.1% (p<0.0001) vs the Not LAF group, but increased at a greater rate (4.0% vs 0.9%/2 years, p<0.0001). Conclusions: Lone AF, compared to non-lone AF, is associated with a lower rate of death, stroke or embolism, recurrence and progression to chronic AF. Interestingly, LV mass increased significantly only in the Lone AF group.


Diabetologia ◽  
2019 ◽  
Vol 63 (3) ◽  
pp. 508-518 ◽  
Author(s):  
Casey Crump ◽  
Jan Sundquist ◽  
Kristina Sundquist

Abstract Aims/hypothesis Preterm birth (gestational age <37 weeks) has been associated with insulin resistance early in life. However, no large population-based studies have examined risks of type 1 and type 2 diabetes and potential sex-specific differences from childhood into adulthood. Clinicians will increasingly encounter adults who were born prematurely and will need to understand their long-term risks. We hypothesised that preterm birth is associated with increased risks of type 1 and type 2 diabetes into adulthood. Methods A national cohort study was conducted of all 4,193,069 singletons born in Sweden during 1973–2014, who were followed up for type 1 and type 2 diabetes identified from nationwide diagnoses and pharmacy data to the end of 2015 (maximum age 43 years; median age at the end of follow-up 22.5 years). Cox regression was used to adjust for potential confounders, and co-sibling analyses assessed the influence of shared familial (genetic and/or environmental) factors. Results In 92.3 million person-years of follow-up, 27,512 (0.7%) and 5525 (0.1%) people were identified with type 1 and type 2 diabetes, respectively. Gestational age at birth was inversely associated with both type 1 and type 2 diabetes risk. Adjusted HRs for type 1 and type 2 diabetes at age <18 years associated with preterm birth were 1.21 (95% CI, 1.14, 1.28) and 1.26 (95% CI, 1.01, 1.58), respectively, and at age 18–43 years were 1.24 (95% CI, 1.13, 1.37) and 1.49 (95% CI, 1.31, 1.68), respectively, compared with full-term birth. The associations between preterm birth and type 2 (but not type 1) diabetes were stronger among females (e.g. at age 18–43 years, females: adjusted HR, 1.75; 95% CI, 1.47, 2.09; males: 1.28; 95% CI, 1.08, 1.53; p < 0.01 for additive and multiplicative interaction). These associations were only partially explained by shared genetic or environmental factors in families. Conclusions/interpretation In this large national cohort, preterm birth was associated with increased risk of type 1 and type 2 diabetes from childhood into early to mid-adulthood. Preterm-born children and adults may need early preventive evaluation and long-term monitoring for diabetes.


Author(s):  
Collier A ◽  
Hair M ◽  
Cameron L ◽  
Ghosh S ◽  
Boyle J ◽  
...  

Background: This study investigated the effects of age, gender, socio-economic status, smoking status, hypertension, ischaemic heart disease, Body Mass Index (BMI), Glycaemic control (HbA1c) and dyslipidaemia in type 2 diabetes in a population-based analysis.


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