Gender differences in antithrombotic treatment in patients with atrial fibrillation from Spain versus the rest of Western Europe. GLORIA-AF Program.

BACKGROUND AND OBJECTIVE: Thromboembolic risk is higher in women than men with non-valvular atrial fibrillation (NVAF). Published data indicate variability in antithrombotic use by gender and region. We analyzed gender-specific antithrombotic treatment patterns in Spain and rest of Western Europe (rWE) in patients with NVAF. METHODS: GLORIA-AF (Phase III) is a global, prospective, observational study which enrolled newly diagnosed NVAF patients with CHA2DS2-VAScs≥1 (2014-2016). Analyses were performed comparing antithrombotic treatments by gender in Spain and rWE. RESULTS: This analysis included 1163 and 7972 patients from Spain and rWE, respectively. Stroke risk was higher in women than men in both Spain and rWE. While in rWE, bleeding risk and antithrombotic treatment pattern were similar between genders, in Spain bleeding risk in women was lower and more females compared to men received OACs (95.0% versus 92.4%, d=-0.1078, respectively). Fewer Spanish patients received direct oral anticoagulants (DOACs) (women 32.1%, men 25.3%) than vitamin-K-antagonists (VKAs) (women 63.0%, men 67.1%) vs. rWE patients. In Spain women received more DOACs compared to men (56.0% versus 44.0%). CONCLUSIONS: OAC rates were higher in Spain as compared to rWE. More women received OACs in Spain, while in rWE no difference by gender was observed. DOACs in rWE are the most prescribed OAC while in Spain, due to prescription barriers, its use remains low for both genders and VKAs are preferred. Spanish women received more DOACs compared to men. (NCT01468701).

Safety of digoxin in nonagenarian patients with atrial fibrillation: lessons from the Spanish Multicenter Registry.

BACKGROUND: The association between digoxin and mortality is an unclear issue. In older patients with atrial fibrillation (AF), where use of digoxin is frequent, the evidence of its safety is scarce. Our aim is to assess the safety of digoxin in nonagenarian patients with AF. METHODS: We evaluated data from 795 nonagenarian patients with non-valvular AF from the Spanish Multicenter Registry. We analyzed the relationship between digoxin and all-cause mortality with the Cox proportional-hazards model. RESULTS: Follow-up was 27.7 ± 18.3 months. Mean age was 92.5 ± 3.8 years, and 71% of nonagenarian patients were female. Digoxin was not associated with increased risk of mortality [adjusted hazard ratio (aHR) = 1.16, 95% CI: 0.96-1.41,P = 0.130]. However, we found a significant increase in mortality in the subgroup with estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m 2 (aHR = 2.01, 95% CI: 1.13-3.57,P = 0.018), but not in the other subgroups of eGFR (30-59 mL/min per 1.73 m2 and ≥ 60 mL/min per 1.73 m2). When exploring the risk of mortality according to sex, male subgroup was associated with an increase in mortality (aHR = 1.48, 95% CI: 1.02-2.14,P = 0.041). This was not observed in females subgroup (aHR = 1.03, 95% CI: 0.81-1.29,P = 0.829). Based on the presence or absence of heart failure, we did not find significant differences (aHR = 1.20, 95% CI: 0.87-1.65,P = 0.268 vs. aHR = 1.15, 95% CI: 0.90-1.47,P = 0.273, respectively). CONCLUSIONS: In our large registry of nonagenarian patients with AF, we did not find an association between digoxin and mortality in the total sample. However, in the subgroup analyses, we found an increase in mortality with the use of digoxin in men and in patients with an eGFR < 30 mL/min per 1.73 m 2.

Clinical Outcomes Following Urgent vs. Elective Percutaneous Mitral Valve Repair.

AIM: To examine procedural and clinical outcomes among patients undergoing percutaneous mitral valve repair (PMVR) within an admission for acute-decompensated heart failure (ADHF). METHODS AND RESULTS: Prospective registry of all consecutive patients with symptomatic mitral regurgitation (MR) grade 3+ or 4+ who underwent PMVR our centre and classified in 2 groups: elective group and urgent PMVR group (within the index admission for ADHF). Echocardiographic, procedural and clinical outcomes were compared between groups. 85 patients (median age 77.0 [67.8-83.4] years, 64.7% male) were treated within the recruitment period. Among them, 17 (20%) underwent urgent MitraClip®. Urgent PMVR were at a higher risk for conventional surgery (p = 0.002) and had worse estimated prognosis according to HF risk scores (p < 0.001). Overall technical success was 100%, without differences between groups. At 30 days, no differences were found in mortality, MR reduction and in NYHA functional improvement between groups. Cumulative estimated survival free from all-cause death was 92.9% (82.4% vs. 95.6%), 89.4% (82.4% vs. 91.1%), 76.3% (82.4 vs. 74.9%) at 6 months, 1-year and 2-years, respectively, with no significant differences between urgent or elective PMVR (p = 0.769). CONCLUSION: MitraClip® implantation can be considered as an urgent therapy during admission for ADHF.

Incidence, predictors of bleeding and prognosis of bleeding in anticoagulated nonagenarian patients with atrial fibrillation.

BACKGROUND: The prevalence of atrial fibrillation (AF) increases with age. The prescription of anticoagulation in very elderly patients is controversial and sometimes underused. Our objective is to report the incidence and predictors of major bleeding in anticoagulated nonagenarian patients with non valvular atrial fibrillation (NVAF). METHODS: We analyzed a large multicentre registry of anticoagulated nonagenarian patients diagnosed with NVAF from three health areas of Spain, between 2013 and 2017. Predictors of major bleeding were studied with a competing risk analysis and the impact of major bleeding with a time-dependent mortality analysis. RESULTS: The incidence rate of major bleeding was 5 per100 person-year (95% Confidence Interval [CI]: 4.59-6.35), similar in the group of patients with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOAC). In the VKAs group we found as predictors of major bleeding: previous admission for bleeding (sub-distribution hazard ratio [sHR] 3.25, 95% CI: 1.48-7.13), creatinine (sHR 1.38, 95% CI: 1.16-1.64,) and control out-of-range INR (sHR 1.90, 95% CI: 1.02-3.55). In DOAC group, male sex (sHR 1.92, 95% CI: 1.18-3.13) and the history of previous admission for bleeding (sHR 2.60, 95% CI 1.33-5.06) were found as a predictor. The HAS-BLED was not associated with major bleeding. Major bleeding was associated with increased mortality in both VKAs and DOAC groups without significant differences. CONCLUSIONS: We found an incidence rate of major bleeding with relative low values, similar in those treated with VKAs and those treated with DOAC, with different predictors of major bleeding in each group. Major bleeding was associated with increased mortality, with no significant difference by oral anticoagulation therapy (OAT).

Prognostic Value of Late Gadolinium Enhancement for the Prediction of Cardiovascular Outcomes in Dilated Cardiomyopathy: An International, Multi-Institutional Study of the MINICOR Group.

BACKGROUND: Dilated cardiomyopathy is associated with increased risk of major cardiovascular events. Late gadolinium enhancement (LGE) cardiac magnetic resonance imaging is a unique tissue-based marker that, in single-center studies, suggests strong prognostic value. We retrospectively studied associations between LGE presence and adverse cardiovascular events in patients with dilated cardiomyopathy in a multicenter setting as part of an emerging global consortium (MINICOR [Multi-Modal International Cardiovascular Outcomes Registry]). METHODS: Consecutive patients with dilated cardiomyopathy referred for cardiac magnetic resonance (2000-2017) at 12 institutions in 4 countries were studied. Using multivariable Cox proportional hazard and semiparametric Fine and Gray models, we evaluated the association between LGE and the composite primary end point of all-cause mortality, heart transplantation, or left ventricular assist device implant and a secondary arrhythmic end point of sudden cardiac death or appropriate implantable cardioverter-defibrillator shock. RESULTS: We studied 1672 patients, mean age 56±14 years (29% female), left ventricular ejection fraction 33±11%, and 25% having New York Heart Association class III to IV; 650 patients (39%) had LGE. During 2.3 years (interquartile range, 1.0-4.3) follow-up, 160 patients experienced the primary end point, and 88 experienced the arrhythmic end point. In multivariable analyses, LGE was associated with 1.5-fold (hazard ratio, 1.45 [95% CI, 1.03-2.04]) risk of the primary end point and 1.8-fold (hazard ratio, 1.82 [95% CI, 1.20-3.06]) risk of the arrhythmic end point. Primary end point risk was increased in patients with multiple LGE patterns, although arrhythmic risk was higher among patients receiving primary prevention implantable cardioverter-defibrillator and widening QRS. CONCLUSIONS: In this large multinational study of patients with dilated cardiomyopathy, the presence of LGE showed strong prognostic value for identification of high-risk patients. Randomized controlled trials evaluating LGE-based care management strategies are warranted.

Vitamin K Antagonists and Direct Oral Anticoagulants in Nonagenarian Patients With Atrial Fibrillation.

OBJECTIVES: Nonagenarian patients are underrepresented in clinical trials that have evaluated oral anticoagulation in patients with atrial fibrillation (AF). The aim of this study was to assess the pronostic impact of oral anticoagulation in patients with AF age ≥90 years. DESIGN: Retrospective multicenter study of nonagenarian patients with AF. SETTING AND PARTICIPANTS: A total of 1750 nonagenarian inpatients and outpatients with nonvalvular AF between January 2013 and December 2018 in 3 Spanish health areas were studied. METHODS: Patients were divided into 3 groups based on antithrombotic therapy: nonoral anticoagulants (30.5%), vitamin-K antagonists (VKAs; 28.6%), and direct oral anticoagulants (DOACs; 40.9%). During a mean follow-up of 23.6 ± 6.6 months, efficacy outcomes (death and embolic events) were evaluated using a Cox regression analysis and safety outcomes (bleeding requiring hospitalization) by competing-risk regression. Results were complemented with a propensity score matching analysis. RESULTS: During follow-up, 988 patients died (56.5%), 180 had embolic events (10.3%), and 186 had major bleeding (10.6%). After multivariable adjustment, DOACs were associated with a lower risk of death and embolic events than nonanticoagulation [hazard ratio (HR) 0.75, 95% confidence interval (CI)] 0.61‒0.92), but VKAs were not (HR 0.87, 95% CI 0.72‒1.05). These results were confirmed after propensity score matching analysis. For bleeding, both DOACs and VKAs proved to be associated with a higher risk (HR for DOAC 1.43; 95% CI 0.97‒2.13; HR for VKA 1.94; 95% CI 1.31‒2.88), although findings for DOACs were not statistically significant (P = .074). For intracranial hemorrhage (ICH), only VKAs-not DOACs-presented a higher risk of ICH (HR 4.43; 95% CI 1.48‒13.31). CONCLUSIONS AND IMPLICATIONS: In nonagenarian patients with AF, DOACs led to a reduction in mortality and embolic events in comparison with nonanticoagulation. This reduction was not observed with VKAs. Although both DOACs and VKAs increased the risk of bleeding, only VKAs were associated with higher ICH rates.

Incidence and prognostic implications of late bleeding events after percutaneous mitral valve repair.

OBJECTIVES: MitraClip is an established therapy for patients with mitral regurgitation (MR) that are considered of high-risk or inoperable. However, late bleeding events (BE) after hospital discharge and their impact on prognosis in this cohort of patients have been poorly investigated. Our purpose is to address the incidence, related factors and clinical implications of BE after hospital discharge in patients treated with MitraClip. METHODS: Prospective registry of all consecutive patients (n = 80) who underwent MitraClip implantation in our Institution between June 2014 and December 2017. BE were defined according to MVARC definitions. A combined clinical end-point including admission for heart failure (HF) and all-cause mortality was established to analyze prognostic implications of BE. RESULTS: During a median follow up of 523.5 days, 41 BE were reported in 21 patients. Atrial fibrillation (AF, HR 4.54, CI95% 1.20-17.10) and combined antithrombotic therapy at discharge (HR 3.52, CI95% 1.03-11.34) were independently associated with BE. In the study period, 15 (18.8%) patients died, 20 (25%) were admitted for HF and 29 (36.3%) presented the combined end-point. After multivariable adjustment BE remained independently associated with an adverse outcome (HR 3.80, CI 95% 1.66-8.72). In the subgroup of patients with AF, HAS-BLED score was higher among subjects with BE (3.1 ±â€¯1.3 vs 2.1 ±â€¯0.9, p = 0.003). HAS-BLED score had a significant discrimination power for the occurrence BE (AUC: 0.677 [0.507-0.848]) in this subgroup. CONCLUSIONS: BE are common after MitraClip and are associated with an impaired outcome. Strategies to reduce bleeding events are paramount in this cohort of patients.

Overview of mitral regurgitation in Europe: results from the European Registry of mitral regurgitation (EuMiClip).

Aims: To determine the prevalence of mitral regurgitation (MR) in a large cohort of consecutive patients undergoing clinically indicated echocardiography and to examine the distribution of primary and secondary MR. Methods and results: All patients undergoing an echocardiographic study in 19 European centres within a 3-month period were prospectively included. MR assessment was performed as recommended by the European Association of Cardiovascular Imaging (EACVI). MR was classified according to mechanism as primary or secondary and aetiologies were reported. A total of 63 463 consecutive echocardiographic studies were reviewed. Any degree of MR was described in 15 501 patients. Concomitant valve disease of at least moderate grade was present in 28.5% of patients, being tricuspid regurgitation the most prevalent. In the subgroup of moderate and severe MR (n = 3309), 55% of patients had primary MR and 30% secondary MR. Both mechanisms were described in 14% of the studies. According to Carpentier's classification, 26.7% of MR were classified as I, 19.9% of MR as II, 22.4% of MR as IIIa, and 31.1% of MR as IIIb. Conclusion: To date, this is the largest echocardiography-based study to analyse the prevalence and aetiology distribution of MR in Europe. The burden of secondary MR was higher than previously described, representing 30% of patients with significant MR. In our environment, degenerative disease is the most common aetiology of primary MR (60%), whereas ischaemic is the most common aetiology of secondary MR (51%). Up to 70% of patients with severe primary MR may have a Class I indication for surgery. However, the optimal therapeutic approach for secondary MR remains uncertain.

Prevalence of optimal valve morphology for MitraClip in patients with mitral regurgitation.

AIMS: To evaluate how often patients with moderate-to-severe or severe mitral regurgitation (MR) meet the anatomical criteria for MitraClip implant and to examine the role of transthoracic echocardiography (TTE) for this task. METHODS AND RESULTS: From February to June 2015, all patients undergoing a TTE in nine Spanish hospitals were prospectively included. Patients with moderate-to-severe and severe mitral regurgitation were selected for analysis. Anatomical eligibility criteria for MitraClip were defined according to the EVEREST trial. A total of 39 855 consecutive TTE were reviewed, and 1403 patients with moderate-to-severe and severe MR were finally included. Primary MR was found in 779 patients (56%). Only in 74 patients (16%), all anatomical criteria for MitraClip could be assessed by TTE. Of these, 56% of patients had optimal valve morphology. Secondary MR was described in 361 patients (26%), and at least 249 of these (69%) had a high surgical risk. All five criteria for MitraClip were adequately assessed by TTE in 299 patients (83%). Of them, 118 patients (39%) had optimal valve morphology. CONCLUSIONS: A considerable proportion of patients have optimal mitral valve morphology for MitraClip. Moreover, TTE was particularly useful in determining whether or not the anatomical criteria for MitraClip implant were met in the majority of patients with secondary MR but in only a minority of those with primary MR.

Frequency, Mechanism and Severity of Mitral Regurgitation: Are There any Differences Between Primary and Secondary Mitral Regurgitation?

BACKGROUND AND AIM OF THE STUDY: Although mitral regurgitation (MR) is a well-recognized prognosis factor, its true prevalence is probably underestimated and its etiology and mechanisms have not been sufficiently explored. The study aim was to evaluate the burden of MR, focusing attention on its frequency, severity, etiology, mechanism, and other associated conditions. METHODS: Between February and June 2015, a total of 39,855 consecutive echocardiographic studies was performed at nine tertiary hospitals, and were prospectively included in the study. MR severity was graded into four groups, ranging from none or trace to severe MR, in accordance with the recommendations of the European Association of Cardiovascular Imaging. Patients with moderate to severe MR were selected for the analysis. RESULTS: MR was detected in 22.6% of cases. MR severity was mild in 82.5% of patients (n = 7,376), moderate in 11.7% (n = 1,048), and severe in 5.8% (n = 521). Concomitant valvular heart disease was present in 3,544 patients (39.7%), with tricuspid regurgitation the most frequently encountered (21.6%). Among moderate and severe MR, primary MR was more frequent than secondary MR (58.8% versus 23.5%), with degenerative valve disease being the most common cause of primary MR (49.2%). A third group composed of mixed forms of MR was described in 17.8% of cases. CONCLUSIONS: MR is a common finding on echocardiography, and is frequently associated with other valvular heart disease. Most MRs are of degenerative origin. The primary and secondary forms of MR differ significantly in their clinical presentation with regard to gender, age, and ventricular function. There appears to be a gap for a 'mixed' group, though further studies are needed to confirm this suggestion.

P2Y12 platelet reactivity after thrombolytic therapy for ST-segment elevation myocardial infarction.

INTRODUCTION: Thrombolysis, as reperfusion therapy for ST segment elevation myocardial infarction (STEMI), induces a pro-thrombotic status with enhanced platelet activity; this study aims to evaluate P2Y12 platelet reactivity and response to clopidogrel in the post-thrombolysis scenario. MATERIALS AND METHODS: Observational, prospective study, including consecutive patients with elective angiography after thrombolytic therapy for STEMI. Every patient received antiplatelet therapy with loading doses of 250 mg aspirin and 300 mg clopidogrel on admission followed by 100mg aspirin and 75 mg clopidogrel daily. P2Y12-dependent platelet reactivity (expressed in P2Y12-Reaction Units, PRU) was assessed with VerifyNow® device on admission, daily after thrombolysis and pre-angiography. RESULTS: 41 patients fulfilled the inclusion criteria. Median time between thrombolysis and angiography was 2,5 days (IQR 1,8-4,1). Post-treatment platelet reactivity (PPR) showed poor correlation with time on clopidogrel treatment (r2=0.04) and reached a maximum value of 274 ± 84 PRU during the first 24h after thrombolysis (Day +1 determination). After this, values showed a progressive reduction until the point of angiography (249 ± 82 PRU), without significant differences between consecutive time-points (p=0,549). Inhibition of platelet aggregation (IPA) assessed as a percentage of P2Y12 receptor blockage was poor, increasing gradually from 0 ± 4% on admission to 11 ± 6% the day of the angiography (p=0,001). 71,4% of patients showed PPR ≥ 208 PRU during angiography. CONCLUSIONS: Platelet reactivity, as assessed by post-treatment P2Y12 mediated reactivity, is heightened after thrombolytic therapy during STEMI management. In this scenario, standard doses of clopidogrel did not achieve significant inhibition of ADP-mediated platelet reactivity.

Post-treatment platelet reactivity predicts long-term adverse events better than the response to clopidogrel in patients with non-ST-segment elevation acute coronary syndrome.

INTRODUCTION AND OBJECTIVES: Poor response to antiplatelet therapy has been associated with adverse long-term outcomes. The objective of this study is to assess the relationship between response to clopidogrel and post-treatment platelet reactivity (PPR) and 1-year major adverse cardiovascular events (MACE) in patients with non-ST segment elevation acute coronary syndrome (NSTEACS). METHODS: Patients with NSTEACS undergoing early coronary angiography were enrolled in this prospective, observational study. The VerifyNow analyzer was used to measure clopidogrel response and PPR immediately before coronary angiography. RESULTS: Of the 179 patients included (97 percutaneous coronary intervention, 21 coronary artery bypass graft), 161 (90%) completed 1-year follow-up and 18 (11%) incurred MACE: 10 deaths, 6 myocardial infarctions, 2 strokes, 5 revascularizations. Lower response to clopidogrel (31 +/- 21% vs. 43 +/- 21%; P.049) and higher PPR (204 +/- 60 vs. 155 +/- 67 platelet reaction units [PRU]; p= 0.006) were significantly associated with MACE occurrence. Multivariate analysis confirmed PPR (OR per 10-unit increase: 1.12, 95%CI: 1.01-1.24; P.020) as an independent predictor of MACE. A PPR cut-off value of 175 PRU was associated with an adjusted OR for 1-year MACE occurrence of 3.9 (95%CI: 1.2-15.4; P.024). CONCLUSIONS: PPR predicts adverse long-term outcomes better than response to clopidogrel in patients with NSTEACS. Patients with PPR values above 175 PRU were identified as being at higher risk for adverse long-term events.

Diastolic time - frequency relation in the stress echo lab: filling timing and flow at different heart rates.

UNLABELLED: A cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been recently validated. Second heart sound can be simultaneously recorded in order to quantify both systole and diastole duration. AIMS: 1- To assess the feasibility and extra-value of operator-independent, force sensor-based, diastolic time recording during stress. METHODS: We enrolled 161 patients referred for stress echocardiography (exercise 115, dipyridamole 40, pacing 6 patients).The sensor was fastened in the precordial region by a standard ECG electrode. The acceleration signal was converted into digital and recorded together with ECG signal. Both systolic and diastolic times were acquired continuously during stress and were displayed by plotting times vs. heart rate. Diastolic filling rate was calculated as echo-measured mitral filling volume/sensor-monitored diastolic time. RESULTS: Diastolic time decreased during stress more markedly than systolic time. At peak stress 62 of the 161 pts showed reversal of the systolic/diastolic ratio with the duration of systole longer than diastole. In the exercise group, at 100 bpm HR, systolic/diastolic time ratio was lower in the 17 controls (0.74 +/- 0.12) than in patients (0.86 +/- 0.10, p < 0.05 vs. controls). Diastolic filling rate increased from 101 +/- 36 (rest) to 219 +/- 92 ml/m2* s-1 at peak stress (p < 0.5 vs. rest). CONCLUSION: Cardiological systolic and diastolic duration can be monitored during stress by using an acceleration force sensor. Simultaneous calculation of stroke volume allows monitoring diastolic filling rate.Stress-induced "systolic-diastolic mismatch" can be easily quantified and is associated to several cardiac diseases, possibly expanding the spectrum of information obtainable during stress.