Very Elderly Patients With Atrial Fibrillation Treated With Edoxaban: Impact of Frailty on Outcomes.

Background: Age and frailty are associated with underuse of anticoagulation in elderly patients with atrial fibrillation (AF). Objectives: This study aimed at assessing major clinical outcomes in very elderly patients with AF treated with recommended dose edoxaban and look for a possible relation with frailty measured by a validated score. Methods: This prospective multicenter cohort study enrolled consecutive very elderly (age ≥80 years) anticoagulation-naïve patients starting recommended doses of edoxaban. Upon entry into the study, patients were categorized into nonfrail, prefrail and frail with the SHARE-FI (Survey of Health, Ageing, and Retirement in Europe-Frailty Index) score. The primary outcome was a composite incidence of stroke/systemic embolism, major bleeding, clinically relevant nonmajor bleeding, and death between frail and fitter patients over 2 years follow-up. Secondary outcomes were frailty-related incidence of the individual components part of the composite outcome. Results: Of the 180 screened patients, 176 were enrolled in the study. Of these, 58 (32.9%) were frail, 35 (19.8%) prefrail, and 83 (47.2%) nonfrail. The composite outcome occurred in 49 patients (18.9% per patient-year). No difference in the primary endpoint between frail and fitter patients (incidence rate ratio: 1.2; 95% CI: 0.6-2.2) was observed. On multivariable analysis, anemia was significantly related to the primary outcome (HR: 3.6; 95% CI: 1.8-7.3; P < 0.001), while frailty was not (frail vs nonfrail HR: 0.9; 95% CI: 0.5-1.8). No difference across frailty categories of the individual components of composite events was observed, except for death. Conclusions: Anticoagulation with recommended dose edoxaban is feasible in very elderly patients with AF even if frail. (ESCAPE [Edoxaban and Frailty in Senior Individuals]; NCT03524924).

Role of New Technologies in Supporting the Treatment of Complex Patients.

Cardiology represents one of the privileged disciplinary areas for the experimentation and validation of the applications of telemedicine. Telemedicine, and the health technologies that go by the name of eHealth, identify the digital exchange of social and health information in order to support and optimize the care process remotely. Telemonitoring applied to cardiovascular diseases is defined as the recording, remote transmission, storage, and interpretation of cardiovascular parameters and diagnostic images. Meta-analyses have shown that telemedicine-supported models of care not only are effective but also cost-effective.

Screening of unknown atrial fibrillation through handheld device in the elderly.

OBJECTIVE: To estimate the prevalence of unknown atrial fibrillation (AF) in the elderly population of the Veneto Region, Italy. METHODS: 1820 patients aged ≥ 65 years with no history of AF and not anticoagulated were enrolled in primary-care settings. They underwent an opportunistic electrocardiogram screening with a handheld device (MyDiagnostick) designed to specifically detect AF. The electrocardiogram recordings were reviewed by the researchers, who confirmed the presence of AF. RESULTS: The device detected an arrhythmia in 143 patients, which was confirmed as AF in 101/143 (70.6%), with an overall prevalence of AF of 5.5% (101/1820). Prevalence of unknown AF resulted in 3.6% in patients aged 65-74 years, and 7.5% in patients age 75 or older, and increased according to CHA2DS2-VASc score: 3.5% in patients with a score of 1 or 2, 5.6% in patients with a score of 3, 7.0% in patients with a score of 4, and 7.2% in patients with a score ≥ 5. The detection rate was significantly higher in patients with mild symptoms compared to asymptomatic counterparts (24.1% vs. 4.0%, P < 0.0001). At multivariate analysis, congestive heart failure and age ≥ 75 years-old were independent predictors for screen-detected AF. CONCLUSIONS: An opportunistic screening with handheld device revealed an unexpectedly high prevalence of unknown AF in elderly patients with mild symptoms. Prevalence increased with age and CHA2DS2-VASc score.

Warfarin, but not rivaroxaban, promotes the calcification of the aortic valve in ApoE-/- mice.

INTRODUCTION: Vitamin K antagonists, such as warfarin, are known to promote arterial calcification through blockade of gamma-carboxylation of Matrix-Gla-Protein. It is currently unknown whether other oral anticoagulants such as direct inhibitors of Factor Xa can have protective effects on the progression of aortic valve calcification. AIMS: To compare the effect of warfarin and rivaroxaban on the progression of aortic valve calcification in atherosclerotic mice. RESULTS: 42 ApoE-/- mice fed with Western-type Diet (WTD) were randomized to treatment with warfarin (n = 14), rivaroxaban (n = 14) or control (n = 14) for 8 weeks. Histological analyses were performed to quantify the calcification of aortic valve leaflets and the development of atherosclerosis. The analyses showed a significant increase in valve calcification in mice treated with warfarin as compared to WTD alone (P = .025) or rivaroxaban (P = .005), whereas no significant differences were found between rivaroxaban and WTD (P = .35). Quantification of atherosclerosis and intimal calcification was performed on the innominate artery of the mice and no differences were found between the 3 treatments as far as atherogenesis and calcium deposition is concerned. In vitro experiments performed using bovine interstitial valve cells (VIC) showed that treatment with rivaroxaban did not prevent the osteogenic conversion of the cells but reduce the over-expression of COX-2 induced by inflammatory mediators. CONCLUSION: We showed that warfarin, but not rivaroxaban, could induce calcific valve degeneration in a mouse model of atherosclerosis. Both the treatments did not significantly affect the progression of atherosclerosis. Overall, these data suggest a safer profile of rivaroxaban on the risk of cardiovascular disease progression.

RANKL Expression Is Increased in Circulating Mononuclear Cells of Patients with Calcific Aortic Stenosis.

We aimed to investigate whether the expression of the OPG/RANK/RANKL triad in peripheral blood mononuclear cells (PBMC) and circulating levels of markers of ectopic mineralization (OPG, FGF-23, PPi) are modified in patients with calcific aortic valve disease (CAVD). We found that patients affected by CAVD (n = 50) had significantly higher circulating levels of OPG as compared to control individuals (p = 0.003). No differences between the two groups were found in FGF-23 and PPi levels. RANKL expression was higher in the PBMC from CAVD patients (p = 0.018) and was directly correlated with the amount of valve calcification (p = 0.032). In vitro studies showed that treatment of valve interstitial cells (VIC) with RANKL plus phosphate was followed by increase in matrix mineralization (p = 0.001). In conclusion, RANKL expression is increased in PBMC of patients with CAVD, is directly correlated with the degree of valve calcification, and promotes pro-calcific differentiation of VIC.

Lipoprotein-associated phospholipase A2 activity predicts cardiovascular events in high risk coronary artery disease patients.

OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is deemed to play a role in atherosclerosis and plaque destabilization as demonstrated in animal models and in prospective clinical studies. However, most of the literature is either focused on high-risk, apparently healthy patients, or is based on cross sectional studies. Therefore, we tested the hypothesis that serum Lp-PLA2 mass and activity are useful for predicting cardiovascular (CV) events over the coronary atherosclerotic burden and conventional risk factors in high-risk coronary artery disease patients. METHODS AND RESULTS: In a prospective cohort study of 712 Caucasian patients, who underwent coronary angiography and measurement of both Lp-PLA2 mass and activity at baseline, we determined incident CV events at follow-up after splitting the patients into a high and a low Lp-PLA2 mass and activity groups based on ROC analysis and Youden index. Kaplan-Meier and propensity score matching analysis were used to compare CV event-free survival between groups. Follow-up data were obtained in 75% of the cohort after a median of 7.2 years (range 1-12.7 years) during which 129 (25.5%) CV events were observed. The high Lp-PLA2 activity patients showed worse CV event-free survival (66.7% vs. 79.5%, p = 0.023) and acute coronary syndrome-free survival (75.4% vs. 85.6%, p = 0.04) than those in low Lp-PLA2 group. CONCLUSIONS: A high Lp-PLA2 activity implies a worse CV prognosis at long term follow up in high-risk Caucasian patients referred for coronary angiography.

Determinants of echocardiographic left atrial volume: implications for normalcy.

AIMS: The relative role of multiple determinants of left atrial volume index (LAVi) in athletes and non-athletes is not fully defined. Thus, we decided to prospectively assess the determinants of LAVi in healthy individuals and competitive athletes over a wide age range. METHODS AND RESULTS: Four hundred and eighteen healthy individuals (mean age 41.7 ± 15.6 years, range 16-84, 65% males, 38% competitive athletes) underwent Doppler echocardiography including assessment of LAVi by the biplane area-length method and of left ventricular (LV) diastolic function including the ratio of early diastolic peak LV inflow velocity to peak myocardial early diastolic velocity (E/e'). Mean LAVi was 32.2 ± 9.0 mL/m(2) in the pooled population. LAVi was larger in athletes than in non-athletes (38.9 ± 9.6 mL/m(2) vs. 28.4 ± 5.8 mL/m(2), P < 0.0001). In the pooled population a stepwise multiple linear regression analysis identified LV end-diastolic volume index (LVEDVi) (ß = 0.378, P < 0.0001), LV mass index (LVMi) (ß = 0.260, P < 0.0001), competitive sport activity (ß = 0.258, P < 0.0001), and age (ß = 0.222, P < 0.0001) as independent determinants of LAVi (model R(2) = 0.54, P < 0.0001). By separate analyses, although LVEDVi, age, and LVMi were predictors of LAVi in both groups, body mass index and the E/e' ratio were additional predictors of LAVi only in non-athletes. CONCLUSIONS: In healthy individuals LV size, competitive sport, age, and LV mass are independent determinants of LAVi. Body mass index and the E/e' ratio affect LAVi only in non-athletes. These findings may have practical implications when assessing normalcy of LA size in the clinical setting.

Spontaneous dissections of coronary arteries and acute coronary syndromes: rationale and design of the DISCOVERY, a multicenter prospective registry with a case-control group.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an unusual cause of acute myocardial ischemia that in almost 50% of cases is followed by sudden death. The increasing frequency of SCAD diagnosis may reflect the widespread use of coronary angiography and percutaneous coronary interventions in acute coronary syndromes (ACS). The incidence of SCAD is estimated between 0.1 and 0.28% of all ACS or sudden deaths evaluated by angiography or by anatomical examination, respectively. Most published data available so far deal with single case reports and probably the real incidence of this disease is underestimated. Some predisposing conditions to SCAD are well known and include Marfan syndrome, pregnancy and peripartum state, drug abuse and some anatomical abnormalities of the coronary arteries like aneurysms and severe kinking. The most appropriate therapeutic approach to SCAD is still controversial and decision making is often based on the clinical presentation, extent of dissection and amount of ischemic myocardium. OBJECTIVES AND METHODS: The purpose of this multicenter prospective registry, named DISCOVERY (DISsection of COronary arteries: Veneto and Emilia RegistrY), with a case-control group is to try to assess the role of SCAD in the pathogenesis of ACS. The primary endpoint is the occurrence of major adverse cardiovascular events related to the therapeutic strategy in the acute phase and in the mid-term follow-up. The secondary endpoints are the estimation of the prevalence of SCAD in the pathogenesis of ACS, the association or disassociation of SCAD with presumptive predisposing factors, the appreciation of the timing and extent of multivessel involvement when present, the occurrence of vascular and ocular comorbidities (i.e. carotid dissection and ocular lens abnormalities), the evaluation of the immediate success and the mid-term outcome of percutaneous coronary interventions and the definition of the role of intravascular ultrasound in diagnosis and treatment of SCAD. The enrollment of approximately 50 patients with SCAD is planned. A planned control group of patients of comparable age, sex and clinical presentation will allow us to identify potential peculiar or specific aspects of SCAD in any phase of the disease. CONCLUSION: The DISCOVERY multicenter registry, with a case-control group, is the first large prospective study aimed at assessing the role of SCAD in the pathogenesis of ACS and at identifying the role of different therapeutic strategies in this unusual, multifaceted and probably underestimated pathologic condition.