Prevalence and clinical predictors of inappropriate direct oral anticoagulant dosage in octagenarians with atrial fibrillation.

PURPOSE: Older age is associated with inappropriate dose prescription of direct oral anticoagulants. The aim of our study was to describe the prevalence and the clinical predictors of inappropriate DOACs dosage among octogenarians in real-world setting. METHODS: Data for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation (AF) Research Database (NCT03760874). Of the AF patients aged ≥ 80 who received DOACs treatment, 253 patients were selected. Participants were categorized as appropriate dosage, overdosage, or underdosage. Underdosage and overdosage were, respectively, defined as administration of a lower or higher DOAC dose than recommended in the EHRA consensus. RESULTS: A total of 178 patients (71%) received appropriate DOACs dose and 75 patients (29%) inappropriate DOACs dose; among them, 19 patients (25.6%) were overdosed and 56 (74.4%) were underdosed. Subgroup analysis demonstrated that underdosage was independently associated with male gender [OR = 3.15 (95% IC; 1.45-6.83); p < 0.001], coronary artery disease [OR = 3.60 (95% IC 1.45-9.10); p < 0.001] and body mass index [OR = 1.27 (1.14-1.41); p < 0.001]. Overdosage was independently associated with diabetes mellitus [OR = 18 (3.36-96); p < 0.001], with age [OR = 0.76 (95% IC; 0.61-0.96; p = 0.045], BMI [OR = 0.77 (95% IC; 0.62-0.97; p = 0.043] and with previous bleedings [OR = 6.40 (0.7; 1.43-28); p = 0.039]. There wasn't significant difference in thromboembolic, major bleeding events and mortality among different subgroups. Underdosage group showed a significatively lower survival compared with appropriate dose group (p < 0.001). CONCLUSION: In our analysis, nearly one-third of octogenarians with AF received an inappropriate dose of DOAC. Several clinical factors were associated with DOACs' overdosage (diabetes mellitus type II, previous bleeding) or underdosage (male gender, coronary artery disease, and higher body mass index). Octogenarians with inappropriate DOACs underdosage showed less survival.

Clinical profile of direct oral anticoagulants versus vitamin K anticoagulants in octogenarians with atrial fibrillation: a multicentre propensity score matched real-world cohort study.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and its prevalence increases with age. Few data are available about the clinical performance of direct oral anticoagulant (DOACs) in patients aged ≥ 80 years with AF. The aim of our propensity score matched cohort study was to compare the safety and efficacy of DOACs versus well-controlled VKA therapy among octogenarians with AF in real life setting. Data for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation Research Database (NCT03760874), which includes all AF patients followed by the participating centers, through outpatient visits every 3 to 6 months. The database was queried for AF patients aged ≥ 80 years who received DOACs or VKAs treatment. The primary effectiveness endpoint was the occurrence of thromboembolic events (a composite of stroke, transient ischemic attack, systemic embolism); the primary safety endpoint was the occurrence of major bleeding; the secondary endpoint was all-cause mortality. The database query identified 774 AF patients aged ≥ 80 years treated with VKAs and 279 with DOACs. Propensity score (2:1) matching selected 252 DOAC and 504 VKA recipients. The mean follow-up was 31.07 ± 14.09 months. The incidence rate of thromboembolic events was 13.79 per 1000 person-years [14.80 in DOAC vs 13.34 in VKA group, Hazard Ratio 1.10; 95% confidence interval (CI) 0.49 to 2.45; P = 0.823]. The incidence rate of intracranial hemorrhage (ICH) was 8.06 per 1000 person-years (3.25 in DOAC vs 10.23 in VKA group, HR 0.33; 95% CI 0.07 to 1.45; P = 0.600). Through these incidence rates, we found a positive net clinical benefit (NCB) of DOACs over VKAs, equal to + 9.01. The incidence rate of all-cause mortality was 105.05 per 1000 person-years (74.67 in DOAC vs 118.67 in VKA group, Hazard Ratio 0.65; 95% CI 0.47 to 0.90; P = 0.010). The concomitant use of antiinflammatory drugs (HR 7.90; P < 0.001) were found to be independent predictor of major bleeding. Moreover, age (HR 1.17; P < 0.002) and chronic kidney disease (HR 0.34; P = 0.019) were found to be independently associated with thromboembolic events. In our study no significant difference in terms of both thromboembolic and major bleeding events, but a significant lower incidence of all-cause mortality, was detected in AF patients aged ≥ 80 years treated with DOACs vs VKAs.

CHA2DS2-VASc Score Predicts Adverse Outcome in Patients with Simple Congenital Heart Disease Regardless of Cardiac Rhythm.

Adult patients with simple congenital heart disease (sACHD) represent an expanding population vulnerable to atrial arrhythmias (AA). CHA2DS2-VASc score estimates thromboembolic risk in non-valvular atrial fibrillation patients. We investigated the prognostic role of CHA2DS2-VASc score in a non-selected sACHD population regardless of cardiac rhythm. Between November 2009 and June 2018, 427 sACHD patients (377 in sinus rhythm, 50 in AA) were consecutively referred to our ACHD service. Cardiovascular hospitalization and/or all-cause death were considered as composite primary end-point. Patients were divided into group A with CHA2DS2-VASc score = 0 or 1 point, and group B with a score greater than 1 point. Group B included 197 patients (46%) who were older with larger prevalence of cardiovascular risk factors than group A. During a mean follow-up of 70 months (IQR 40-93), primary end-point occurred in 94 patients (22%): 72 (37%) in group B and 22 (10%, p < 0.001) in group A. Rate of death for all causes was also significantly higher in the group B than A (22% vs 2%, respectively, p < 0.001). Multivariable Cox regression analysis revealed that CHA2DS2-VASc score was independently related to the primary end-point (HR 1.84 [1.22-2.77], p = 0.004) together with retrospective AA, stroke/TIA/peripheral thromboembolism and diabetes. Furthermore, CHA2DS2-VASc score independently predicted primary end-point in the large subgroup of 377 patients with sinus rhythm (HR 2.79 [1.54-5.07], p = 0.01). In conclusion, CHA2DS2-VASc score accurately stratifies sACHD patients with different risk for adverse clinical events in the long term regardless of cardiac rhythm.

Nonvitamin K Antagonist Oral Anticoagulants Use in Patients with Atrial Fibrillation and Bioprosthetic Heart Valves/Prior Surgical Valve Repair: A Multicenter Clinical Practice Experience.

This is an observational study to investigate the efficacy and safety of nonvitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with bioprosthetic valves or prior surgical valve repair in clinical practice. A total of 122 patients (mean age: 74.1 ± 13.2; 54 females) with bioprosthetic heart valve or surgical valve repair and AF treated with NOACs were included in the analysis. The mean CHA2DS2-VASc (Congestive heart failure, Hypertension, Age >75 years, Diabetes mellitus, prior Stroke or transient ischemic attack, Vascular disease) and HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile INR [international normalized ratio], Elderly, Drugs or alcohol) score values were 3.6 ± 1.2 and 2.6 ± 1.4, respectively. Of the total study population, 28.6% was taking apixaban 5 mg twice daily (BID), 24.5% apixaban 2.5 mg BID, 18% dabigatran 150 mg BID, 13% dabigatran 110 mg BID, 9.8% rivaroxaban 20 mg daily (QD), and 5.7% rivaroxaban 15 mg QD. Also, 92% of the study population previously had warfarin replaced with NOACs due to lack compliance and labile INR control (time in therapeutic range < 60%). NOAC therapy for AF was started on average 934 ± 567 days after bioprosthetic heart valve implantation or surgical repair for an average duration of 835 ± 203 days. The study population included 24 (19.6%) patients with bioprosthetic mitral valve, 52 (43%) patients with bioprosthetic aortic valve, 41 (33.6%) patients with previous surgical mitral repair, 5 (4%) patients with previous surgical aortic repair, and concomitant use of NOACs. All patients were evaluated for thromboembolic events (ischemic stroke, transient ischemic attack, systemic embolism) as well as major bleeding events during the follow-up period. In our study population, we recorded a low mean annual incidence of thromboembolism (0.8%) and major bleeding (1.3%). According to our data, anticoagulation therapy with NOACs seems to be an effective and a safe treatment strategy for nonvalvular AF patients with bioprosthetic valves or prior surgical valve repair.

Are aortic coarctation and rheumatoid arthritis different models of aortic stiffness? Data from an echocardiographic study.

BACKGROUND: Patients who underwent a successful repair of the aortic coarctation (CoA) show high risk for cardiovascular (CV) events. Mechanical and structural abnormalities in the ascending aorta (Ao) might have a role in the prognosis of CoA patients. We analyzed the elastic properties of Ao measured as aortic stiffness index (AoSI) in CoA patients in the long-term period and we compared AoSI with a cohort of 38 patients with rheumatoid arthritis (RA) and 38 non-RA matched controls. METHODS: Data from 19 CoA patients were analyzed 28 ± 13 years after surgery. Abnormally high AoSI was diagnosed if AoSI > 6.07% (95th percentile of the AoSI detected in our reference healthy population). AoSI was assessed at the level of the aortic root by two-dimensional guided M-mode evaluation. RESULTS: CoA patients showed more than two-fold higher AoSI compared to RA and controls (9.8 ± 12.6 vs 4.8 ± 2.5% and 3.1 ± 2.0%, respectively; all p < 0.05 and in 5 of 19 patients with CoA (26%) AoSI was exceptionally high. The 5 patients with abnormally high AoSI were older with higher BP, LV mass and prevalence of LV diastolic dysfunction. Multiple linear regression analysis revealed that AoSI was independently related to the presence of LV hypertrophy and higher LV relative wall thickness. CONCLUSIONS: CoA patients have higher AoSI levels than RA patients and non-RA matched controls. AoSI levels are abnormally high in a small sub-group of CoA patients who show a very high-risk clinical profile for adverse CV events.

Value of Combined Circumferential and Longitudinal Left Ventricular Systolic Dysfunction to Predict Adverse Outcome in Patients with Asymptomatic Aortic Stenosis.

BACKGROUND AND AIM OF THE STUDY: Patients with asymptomatic aortic stenosis (AS) may have left ventricular systolic dysfunction (LVSD) defined as an impairment of the circumferential and/or longitudinal (C&L) myocardial fibers, despite a preserved left ventricular ejection fraction (LVEF). An assessment was made as to whether the combined LVSD of C&L fibers has a prognostic impact in asymptomatic AS. METHODS: A total of 200 asymptomatic AS patients was analyzed. Midwall shortening and mitral annular peak systolic velocity were considered as indices of C&L function and classified as low if <16.5% and <8.5 cm/s, respectively. The primary outcome was a composite of major cardiovascular events (MACE), including aortic valve-related and ischemic cardiovascular-related events. RESULTS: During a 25-month follow up period, MACE occurred in 69 patients (35%),while 46 of 72 patients (64%) had C&L LVSD and 23 of 128 patients (18%) had not (p <0.001). Cox analysis identified C&L LVSD as an independent MACE predictor, together with aortic transvalvular peak gradient, E/E' ratio and excessive left ventricular mass. C&L-LVSD also predicted the occurrence of aortic valve-related events and ischemic cardiovascular-related events analyzed separately. A receiver operating characteristic curve analysis showed that the area under the curve (AUC) for C&L LVSD in predicting MACE was 0.77, significantly higher (p = 0.002, z-statistic) than the AUCs of C&L fibers considered individually (0.64 and 0.63, respectively). CONCLUSION: C&L-LVSD provides additional prognostic information into traditional risk factors for patients with asymptomatic AS.

Echocardiographic markers of inducible myocardial ischemia at baseline evaluation preparatory to exercise stress echocardiography.

BACKGROUND: Tissue Doppler Imaging (TDI) is a sensible and feasible method to detect longitudinal left ventricular (LV) systolic dysfunction (LVSD) in patients with diabetes mellitus, hypertension or ischemic heart disease. In this study, we hypothesized that longitudinal LVSD assessed by TDI predicted inducible myocardial ischemia independently of other echocardiographic variables (assessed as coexisting potential markers) in patients at increased cardiovascular (CV) risk. METHODS: Two hundred one patients at high CV risk defined according to the ESC Guidelines 2012 underwent exercise stress echocardiography (ExSEcho) for primary prevention. Echocardiographic parameters were measured at rest and peak exercise. RESULTS: ExSEcho classified 168 (83.6 %) patients as non-ischemic and 33 (16,4 %) as ischemic. Baseline clinical characteristics were similar between the groups, but ischemic had higher blood pressure, received more frequently beta-blockers and antiplatelet agents than non-ischemic patients. The former had greater LV size, lower relative wall thickness and higher left atrial systolic force (LASF) than the latter. LV systolic longitudinal function (measure as peak S') was significantly lower in ischemic than non-ischemic patients (8.7 ± 2.1 vs 9.7 ± 2.7 cm/sec, p = 0.001). The factors independently related to myocardial ischemia at multivariate logistic analysis were: lower peak S', higher LV circumferential end-systolic stress and LASF. CONCLUSIONS: In asymptomatic patients at increased risk for adverse CV events baseline longitudinal LVSD together with higher LV circumferential end-systolic stress and LASF were the factors associated with myocardial ischemia induced by ExSEcho. The assessment of these factors at standard echocardiography might help the physicians for improving the risk stratification among these patients for ExSEcho.

Prevalence and Factors Associated with Subclinical Left Ventricular Systolic Dysfunction Evaluated by Mid-Wall Mechanics in Rheumatoid Arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased cardiovascular event rate, mainly due to the arterial stiffness which leads to coronary atherosclerosis and concentric left ventricular (LV) geometry. These conditions predispose to LV systolic dysfunction (LVSD), which can be detected by stress-corrected mid-wall shortening (sc-MS), an early prognosticator of cardiovascular events in asymptomatic patients with arterial hypertension and/or diabetes. In these subjects, sc-MS is frequently impaired even though LV ejection fraction (LVEF) is preserved. In this study, we analyzed the prevalence and the factors associated with asymptomatic LVSD measured by sc-MS among patients with RA and verified whether RA per se was independently related to LVSD. METHODS: We prospectively recruited 198 outpatients with RA without overt cardiac disease between January and June 2014 and compared them to 198 controls matched for age, gender, body mass index, and prevalence of hypertension and diabetes. sc-MS was taken as index of LVSD and considered impaired if <86.5%. RESULTS: Impaired sc-MS was detected in 110 (56%) RA patients and in 30 (15%) controls (P < 0.001), whereas LVEF was impaired (value <50%) in six (3%) RA patients and in two (1%) controls (P = ns). Multiple logistic regression analysis revealed that RA was independently associated with impaired sc-MS (Exp ß 2.01 [CI 1.12-3.80], P = 0.02) together with increased LV mass and concentric geometry. CONCLUSIONS: More than half RA patients without overt cardiac disease have LVSD detectable by sc-MS. RA emerges as a condition closely related to LVSD. These findings might explain the high risk for adverse cardiovascular events in RA patients.

Does treatment assignment influence the prognosis of patients with symptomatic severe aortic stenosis?

OBJECTIVE: Aortic valve replacement (AVR) is the standard therapy in patients with symptomatic aortic stenosis (AS). In high surgical risk patients, alternative therapeutic options to medical treatment (MT) such as trans-catheter aortic valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) have been proposed. In this study we evaluated whether treatment assignment influences per se the prognosis of these subjects. PATIENTS AND METHODS: Criteria for treatment assignment were based on patient's clinical conditions, Logistic EuroSCORE and other co-morbidities ignored by EuroSCORE. Due to baseline clinical differences between patients with diverse treatment assignment, we used propensity score matching to achieve balance. RESULTS: 368 patients were studied: 141 underwent AVR, 127 TAVI, 49 BAV and 51 MT. 84 events (deaths for all causes) occurred during 14 months of follow-up: 11 AVR (8%), 26 TAVI (20%), 18 MT (35%), 29 BAV group (59%). Traditional Cox analysis identified treatment assignment as independent predictor of events (HR 1.82 [CI 1.10-3.25]) together with lower left ventricular ejection fraction, impaired renal function and history of heart failure. Matched Cox analysis by propensity score confirmed treatment assignment as an independent prognosticator of events (HR 1.90 [CI 1.27-2.85]), and showed similar rate events in TAVI and AVR patients, while it was significantly increased in BAV and MT patients. CONCLUSIONS: Treatment assignment may influence outcome of symptomatic patients with AS.

Analysis of left atrial performance in patients with type 2 diabetes mellitus without overt cardiac disease and inducible ischemia: high prevalence of increased systolic force related to enhanced left ventricular systolic longitudinal function.

OBJECTIVES: In patients with chronic pressure overload, higher left atrial systolic force (LASF) is associated with high-risk cardiovascular (CV) phenotype, with increased left ventricular (LV) mass, concentric hypertrophy, and diastolic dysfunction. In hypertension and aortic stenosis, LASF predicts increased rate of CV events independent of traditional risk factors. Moreover, LASF is an independent predictor of heart failure in diabetic and nondiabetic patients. Limited data are available about LASF and its relationship with LV systolic function in type 2 diabetes mellitus (T2DM). METHODS: We used baseline clinic and echocardiographic data from 333 patients recruited in the SHORTWAVE study evaluating LV and left atrial performance in T2DM patients without cardiac disease. LASF was calculated by Manning's method and defined high when exceeded 16 Kdynes (90th percentile of LASF found in 120 healthy subjects used as controls). RESULTS: Mean LASF was 15.8 Â ± 9.4 Kdynes/cm(2) and showed a close positive correlation with peak mitral annular systolic velocity (function of LV longitudinal fibers), independent of E/E', age, systolic blood pressure, heart rate, and concentric geometry (multiple R = 0.57, P < 0.0001). Such independent correlation (tested in patients with and without concomitant hypertension) was confirmed at multiple logistic regression analysis where patients were dichotomized for having high (119 = 36%) or normal LASF. CONCLUSIONS: High LASF is present in one third of T2DM patients without overt cardiac disease and is positively and independently related to an increased LV longitudinal shortening function, suggesting a close interaction between LV systolic and diastolic function.

Combined circumferential and longitudinal left ventricular systolic dysfunction in patients with asymptomatic aortic stenosis.

BACKGROUND: Early detection of left ventricular (LV) systolic dysfunction is pivotal in the management of patients with aortic stenosis (AS). LV circumferential and/or longitudinal shortening may be impaired in these patients despite LV ejection fraction is preserved. We focused on prevalence and factors associated with combined impairment of circumferential and longitudinal shortening (C&L) in asymptomatic AS patients. METHODS: Echocardiographic and clinical data from 200 patients with asymptomatic AS of any degree without history of heart failure and normal LV ejection fraction were analyzed. C&L were evaluated by mid-wall shortening (MS) and tissue Doppler mitral annular peak systolic velocity (S'), and classified low if <16.5% and if <8.5 cm/sec, respectively (10th percentiles of controls). RESULTS: Combined C&L dysfunction was detected in 72 patients (36%). The variables associated with this condition were higher LV mass (OR 1.02 [CI 1.01-1.04], P = 0.03), concentric LV geometry (OR 4.30 [CI 1.79-10.34], P = 0.001), increasing pulmonary artery wedge pressure (by E/e' ratio; OR 1.11 [CI 1.04-1.19], P = 0.001). The relation of MS and peak S' was linear and slightly significant in the whole population (r = 0.23; F statistic=0.001), absent in patients with C&L dysfunction (r = 0.04; F = ns), negative (linear model) in the subgroup of patients without C&L dysfunction (r = -0.22; F = 0.02). CONCLUSIONS: C&L dysfunction is present in more than one-third of patients with asymptomatic AS and is associated with concentric LV geometry and higher degree of diastolic dysfunction. The relation between MS and peak S' largely varies in the subgroups with different C&L function.

Prevalence and factors related to left ventricular systolic dysfunction in asymptomatic patients with rheumatoid arthritis. A prospective tissue Doppler echocardiography study.

BACKGROUND: Patients with rheumatoid arthritis (RA) have a high risk for cardiovascular disease due to a chronic inflammatory state, accelerated atherosclerosis, and changes in left ventricular (LV) geometry. These conditions predispose patients to LV systolic dysfunction (LVSD). In this study we assessed whether RA is a condition associated with LVSD, and analyzed the prevalence and factors associated with LVSD in patients with RA. PATIENTS AND METHODS: Echocardiographic and clinical data from 198 patients with RA without presence or history of symptoms of cardiac disease were compared with 198 non-RA controls matched for cardiovascular risk factors. LVSD was identified with tissue Doppler echocardiography (TDE) when mitral annular peak systolic velocity (S') was < 9.0 cm/s. RESULTS: Patients with RA were 61 ± 12 years old and 71 % were female (disease duration 14 ± 10 years). LVSD was found in 89 patients with RA (45 %). By multiple regression analysis including both RA patients and controls, RA emerged as an independent condition associated with LVSD (exp ß 3.89; CI: 1.87-8.08) together with higher E/E' ratio (index of LV diastolic function) and diabetes mellitus. For the 198 patients with RA, the variables associated with LVSD were higher E/E' ratio and systolic blood pressure. CONCLUSIONS: Almost half of asymptomatic RA patients without history of cardiac disease have subclinical LVSD easily detectable with TDE. RA is closely related to LVSD. A higher degree of LV diastolic dysfunction and systolic blood pressure are associated with LVSD in these patients, whose risk for cardiovascular events could be better defined using such information in the asymptomatic stage of cardiac disease.

Left atrial work in patients with stable chronic heart failure: factors associated and prognostic role.

BACKGROUND: Limited information is available on left atrial (LA) work in chronic heart failure (CHF) patients. We evaluated correlates and prognostic role of LA work in 243 CHF patients using as reference for normal LA work values 230 healthy controls. METHODS: Left atrial work was assessed by computation of LA kinetic energy (LAKE) from the formula: 0.5 × m × A(2) where m is LA stroke volume × blood density, and A is transmitral Doppler peak atrial velocity. The prespecified primary endpoint of the study was major cardiovascular (CV) events, a composite endpoint defined as CV death + hospitalization for heart failure (HF). RESULTS: Left atrial kinetic energy was 3.9 ± 2.7 in CHF patients and 2.6 ± 1.4 Kdynes/m(2) in controls (P < 0.001). Abnormally high LAKE (>5.4 Kdynes/m(2) = mean + 2 SD of the controls) was found in 19% of CHF patients and 4% of controls (P < 0.001). LAKE was independently associated with an increased shortening of left ventricular (LV) longitudinal fibers and renal dysfunction. CV death or hospitalization for decompensated HF occurred in 66% and 20% of patients with abnormally high and normal LAKE, respectively (P < 0.001). Abnormally high LAKE, not LA size, was an independent predictor of events hazard ratio (HR) 3.92 [95% CI 1.96-7.84] together with renal dysfunction and lower LV ejection fraction. CONCLUSION: In CHF patients, LAKE is significantly higher than in healthy controls, the prevalence of abnormally high LAKE is near fivefold higher in the former than in the latter. LAKE depends on systolic LV and renal function and is a strong predictor of CV death and hospitalization for HF. LA work has an incremental prognostic value over LA size.

Prognostic stratification by conventional echocardiography of patients with aortic stenosis: the "CAIMAN-ECHO score".

BACKGROUND AND AIM: Surgery is not recommended in asymptomatic patients with aortic stenosis (AS). However, prognosis of these patients is worse than retained. We built a simple score (named by the acronym "CAIMAN") for stratifying asymptomatic patients with AS according to the different risk for cardiovascular events. MATERIAL AND METHODS: Data from 141 patients with moderate-to-severe AS followed up for 36 months were analyzed. The end point "outcome" was defined as death of all causes or aortic valve replacement imposed by symptoms or hospital admission for myocardial infarction and/or heart failure. The score was validated in 143 patients prospectively recruited in 2 different centers. RESULTS: The 40 events occurred in the original cohort were associated with higher aortic transvalvular peak jet velocity, calcium score, and observed/predicted left ventricular (LV) mass ratio. Based on the hazard ratios of Cox analysis, the score was calculated as follows: calcium score 1-3 = 1 point, 4 = 6 points; transvalvular peak jet velocity ≤3.6 m/sec = 1 point, 3.6 m/sec = 3 points, observed/predicted LV mass ratio ≤110% = 1 point, >110% = 3 points. After a mean period of 28 ± 18 months, event-free survival was 18%, 42%, 91%, and 96% in the 4 quartiles of echo score. The accuracy of the score in predicting events was 84% and 77% (P = 0.09) in the original and validation cohort, respectively. CONCLUSIONS: The CAIMAN-ECHO score is a simple and feasible tool useful for an accurate prognostic stratification of patients with asymptomatic moderate-to-severe AS.

Oral anticoagulation and VKORC1 polymorphism in patients with a mechanical heart prosthesis: a 6-year follow-up.

Therapy with Vitamin K antagonists (VKA) effectively reduces the thrombosis risk in many clinical conditions. Genetic variants of vitamin K epoxide reductase (VKORC-1) are associated with increased VKA effect and bleeding risk. It is unknown whether these variants could also affect the long-term outcome in patients with high-dosage oral anticoagulation and/or more difficult adherence to the therapeutic INR range. Hundred and twenty-four patients with mechanical heart valve replacement assuming VKA were genotyped for VKORC-1 -1639G>A (Rs9923231) polymorphism. Hemorrhage, venous thrombosis and atherothrombotic events were retrospectively assessed for a 6-year period. Furthermore, stability of their INR in relationship with the VKORC-1 genotype was investigated day-by-day for 3 months. No differences were observed in hemorrhage and venous thrombosis events according to rs 9923231. GG genotype carriers (n = 41) had no atherothrombotic events, while 4 strokes, 4 TIA and 3 AMI were diagnosed in A carriers (n = 83; P = 0.0008). During the daily observation period, A allele carriers had lower VKA requirements (4.7, 3.7, 2.2 mg/day for GG/GA/AA genotype respectively; P = 0.00001), higher mean INR (2.7, 2.8, 2.9; P = 0.05) and a higher number of examinations above the therapeutic range than GG carriers (17 % vs. 0 % in GG genotype, P = 0.036). Conversely, patients with GG genotype had a more stable dosage of VKA (P = 0.006) and a higher percentage of examinations under the therapeutic range (51, 43 and 36 % in GG, GA and AA genotype, respectively, P = 0.040). In patients with high dosage VKA, VKORC-1 polymorphism is associated to a different warfarin dosage, anticoagulation level, time spent outside the therapeutic range and, in the long-term, a different incidence of atherothrombotic events.

Tissue Doppler indices of diastolic function as prognosticator in patients without heart failure in primary care.

BACKGROUND: Tissue Doppler imaging (TDI) indices of left ventricular (LV) diastolic function provide incremental prognostic information on mortality and morbidity in the general population and in several clinical scenarios. Their independent, additional role in outpatients with normal LV ejection fraction (LVEF) and without heart failure (HF) is undefined. METHODS: We reviewed clinical and echocardiographic records of 2628 consecutive outpatients 52.8% male, median age 71 years) with LVEF > 50% without concurrent or prior HF, from the Cardiovascular Center of Trieste. We analyzed septal early mitral annular velocity (e') and its combination with mitral peak early filling velocity (E/e') in relation to the composite end-point of death and cardiovascular hospitalizations. RESULTS: During follow-up of 26 months (interquartile range: 12-41), 392 (15%) patients experienced the endpoint (88 deaths). Increasing E/e' showed an overall association with the clinical end-point (log rank p < 0.02), but with no prognostic difference between the middle and upper tertile. Decreasing e' also showed an association with the end-point, with a more balanced stepwise risk increase for increasing tertiles (log rank p < 0.01 for all contrasts). At multivariable analysis, E/e' (either in tertiles or dichotomized according to the threshold of 15) was no longer associated with clinical outcome, whereas e' independently predicted the combined endpoint [hazard ratio 0.73 (0.53-0.94), p = 0.04]. The prognostic value of e' was incremental to that of other clinical and echocardiographic variables (p = 0.04). CONCLUSIONS: In outpatients with normal LVEF and without HF, e' and E/e' are both associated with clinical end-points, though only e' is an independent and incremental predictor of outcome. These findings suggest a potential role for e' as a prognosticator, and spread a cautionary word about the utilization of septal E/e' alone as a surrogate for a comprehensive assessment of diastolic function in this context.

[The challenge of improving evidence-based therapy adherence in the secondary prevention of coronary artery disease: the next frontier of cardiac rehabilitation]. / Migliorare l'aderenza all'assunzione dei farmaci per la prevenzione secondaria della cardiopatia ischemica: la prossima frontiera della riabilitazione cardiovascolare.

Non-adherence to prescribed drug regimens is an increasing medical problem affecting physicians and patients and contribute to negative outcomes, such as the increased risk of subsequent cardiovascular events. Analysis of various patient populations shows that the choice of drug, its tolerability and the duration of treatment influence the non-adherence. Intervention is required toward patients and health-care providers to improve medication adherence. This review deals about the prevalence of non-adherence to therapy after medical and surgical cardiac event, the risk factors affecting non-adherence and the strategies to implement it. Interventions that may successfully improve adherence should include improved physician compliance with guidelines, patient education and patient reminders, frequent visits or telephone calls from staff, simplification of the patient's drug regimen by reducing the number of pills and daily doses. Since single interventions do not appear efficaceous, it is necessary to establish multiple interventions simultaneously addressing a number of barriers to adherence.

Clinical Benefit of Direct Oral Anticoagulants Versus Vitamin K Antagonists in Patients with Atrial Fibrillation and Bioprosthetic Heart Valves.

PURPOSE: The use of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and bioprosthetic heart valve is still controversial. The aim of this study was to compare the tolerability and effectiveness of treatment with DOACs versus vitamin K antagonists (VKAs) in patients with AF and a bioprosthetic heart valve in clinical practice. METHODS: Data for this study were sourced from the multicenter, prospectively maintained AF Research Database (NCT03760874), which includes all patients with AF undergoing follow-up at participating centers through outpatient visits every 3-6 months. The rates of occurrence of thromboembolic events (ischemic stroke, transient ischemic attack, systemic embolism), major bleed, and intracranial hemorrhage (ICH) were assessed. These data were used for quantifying the net clinical benefit (NCB) of DOACs versus VKAs, in accordance with the following formula: (Thromboembolic events incidence rate with VKAs - Thromboembolic events incidence rate with DOACs) - Weighting factor × (ICH rate with DOACs - ICH incidence rate with VKAs). The database was retrospectively queried for patients with AF who were prescribed a DOAC or VKA and had a history of bioprosthetic heart valve replacement. FINDINGS: A total of 434 patients with AF (DOACs, n = 211; VKAs, n = 223) were identified. Propensity score matching identified 130 patients prescribed DOACs (apixaban, 55.4%; rivaroxaban, 30.0%; dabigatran, 13.1%; edoxaban, 1.4%) and the same number of VKA recipients (warfarin, 89.2%; acenocoumarol, 10.8%). The mean (SD) duration of follow-up was 26.8 (2.3) months. The incidence rates of thromboembolic events were 1.3 per 100 person-years in the DOAC group versus 2.0 per 100 person-years in the VKA group (P = 0.14). The incidence rates of major bleed events were 2.6 per 100 person-years in the DOAC group versus 4.9 per 100 person-years in the VKA group (P = 0.47). The incidence rates of ICH were 0.38 per 100 person-years in the DOAC group versus 1.16 in the VKA group (hazard ratio = 0.33; 95% CI, 0.05-2.34; P = 0.3). A positive NCB of DOACs over VKAs of +1.87 was found. IMPLICATIONS: According to these data from clinical practice, DOACs seem to be associated with a greater NCB versus VKAs in patients with AF with a bioprosthetic heart valve, primarily due to lower rates of both major bleeds and thromboembolic events.

Real-life Performance of Edoxaban in Elderly Patients With Atrial Fibrillation: a Multicenter Propensity Score-Matched Cohort Study.

PURPOSE: The purpose of the current study was to compare the efficacy and safety of edoxaban versus vitamin K antagonist (VKA) therapy among a cohort of elderly patients (ie, those aged ≥75 years) with atrial fibrillation (AF) in a real-life setting. METHODS: A propensity score-matched cohort observational study was performed comparing the safety and efficacy of edoxaban versus VKA therapy among a cohort of elderly (aged ≥75 years) patients with AF in a real-life setting. Follow-up data were obtained through outpatient visits at 1, 3, and every 6 months. The primary safety outcome was major bleeding. The primary efficacy outcome was the composite of stroke, transient ischemic attack, and systemic embolism. FINDINGS: A total of 130 patients receiving edoxaban 60 mg (EDO) treatment were compared with the same number of VKA recipients. The mean follow-up was 16 (2.6) months. The cumulative incidence of thromboembolic events in the EDO and VKA groups was 1.5% (2 of 130) and 2.3% (3 of 130), respectively (P < 0.6). The cumulative incidence of major bleeding events was 1.5% (2 of 130) in the EDO group and 3.1% (4 of 130) in the VKA group (P < 0.4). The total anticoagulant therapy discontinuation rate was 2.3% (3 of 130) in the EDO group and 4.6% (6 of 130) in the VKA group (P < 0.3). A nonsignificant trend in improved adherence was observed between the EDO and VKA groups (81% vs 78%; P = 0.6). IMPLICATIONS: Edoxaban therapy showed a good real-life performance among elderly patients (aged ≥75 years) with AF.

Persistence on apixaban in atrial fibrillation patients: a retrospective multicentre study.

AIMS: Real-world data on treatment persistence, safety and effectiveness of non-Vitamin K antagonist oral anticoagulants (NOACs) play an important role in the assessment of risks and benefits of these drugs. Our aim was to evaluate persistence on treatment, incidence of major bleeding and incidence of a composite endpoint of major events, including all-cause death, myocardial infarction, stroke and systemic thromboembolism, during treatment with apixaban in a cohort of patients with nonvalvular atrial fibrillation (NVAF). METHODS: In this multicentre retrospective observational study, we retrieved data from medical records of five Italian hospitals on patients with a diagnosis of NVAF who initiated apixaban between 1 January 2014 and 31 March 2016 and had a first subsequent visit at the same hospital. RESULTS: We studied 766 patients with mean age of 74.2 (standard deviation 11.1) years and median CHADS2 and CHA2DS2VASc scores of 2.0 and 4.0, respectively. Over a median follow-up period of 339 days, persistence on treatment was 83.5% [95% confidence interval (95% CI) 75.5-89.1%]. The rate of major bleeding (per 100 person-years) was 1.15 (95% CI 0.39-1.90 per 100 person-years), while the cumulative incidence was 4.4% (95% CI 1.6-12.0). The rate of major events was 1.97 (95% CI 1.08-2.86) per 100 patient-years, with a cumulative incidence over the entire follow-up period of 7.7% (95% CI 4.6-12.8). CONCLUSION: In real-life conditions, NVAF patients treated with apixaban show rates of treatment discontinuation and major bleedings, which are comparable to those found in the ARISTOTLE pivotal study, thus supporting its external validity.