Maternal-fetal dyad beyond the phenomenology of pregnancy: from primordial cardiovascular prevention on out, do not miss this boat!

Pregnancy represents a stress test for every woman's cardiovascular (CV) system, and a pre-existing maternal unfavorable cardio-metabolic phenotype can uncover both adverse pregnancy outcomes and the subsequent development of cardiovascular disease (CVD) risk factors during and after pregnancy. Moreover, the maternal cardiac and extracardiac environment can affect offspring's cardiovascular health through a complex mechanism called developmental programming, in which fetal growth can be influenced by maternal conditions. This interaction continues later in life, as adverse developmental programming, along with lifestyle risk factors and genetic predisposition, can exacerbate and accelerate the development of CV risk factors and CVD in childhood and adolescence. The aim of this narrative review is to summarize the latest evidences regarding maternal-fetal dyad and its role on primordial, primary and secondary CV prevention.

Role of CES1 and ABCB1 Genetic Polymorphisms on Functional Response to Dabigatran in Patients with Atrial Fibrillation.

Background: Dabigatran etexilate is a pro-drug hydrolyzed into dabigatran by carboxylesterases (CES) and is a substrate of the P-Glycoprotein encoded by the adenosine-triphosphate-binding cassette sub-family B member (ABCB)1 genes. We evaluated the functional response to dabigatran according to different CES1 and ABCB1 single-nucleotide polymorphisms (SNPs) in patients with atrial fibrillation (AF). Methods: A total of 100 consecutive patients with AF taking dabigatran were enrolled by two Italian centers. A venous blood sample was drawn for genetic determinations, as well as a measurement of the diluted thrombin time (dTT) and drug plasma concentrations, at the trough and peak. The main objective was the relationship between the dTT values and CES1 rs2244613, CES1 rs8192935 and ABCB1 rs4148738 SNP while on two different dabigatran doses (110 and 150 mg BID). Results: A total of 43 patients were on a 110 mg dabigatran dose and 57 on 150 mg. The DTT values at the trough and at peak were not different among patients with different CES1 rs2244613 and CES1 rs8192935 genotypes, regardless of the dabigatran dose. In patients on 150 mg dabigatran, the dTT values at the trough were 77 (44-111) ng/mL in patients with the ABCB1 rs4148738 heterozygous CT genotype vs. 127 (85-147) ng/mL in the wild-type CC genotype vs. 110 (47-159) ng/mL in the mutant trait TT genotype (p = 0.048). In patients with the ABCB1 rs4148738 CT genotype, OR for having dTT values at a trough below the median was 3.21, 95% CI 1.04-9.88 (p = 0.042). Conclusions: ABCB1 rs4148738 CT heterozygous is associated with the reduced anticoagulant activity of dabigatran at the trough in patients receiving the higher dose regimen.

A real-world multicenter study on left atrial appendage occlusion: The Italian multi-device experience.

Background: Transcatheter left atrial appendage occlusion (LAAO) has emerged as an alternative treatment for stroke prevention in patients with atrial fibrillation (AF) at high risk of thromboembolism, who cannot tolerate long-term oral anticoagulation (OAC). Questions persist regarding effectiveness and safety of this treatment and the optimal post-interventional antithrombotic regimen after LAAO. Methods: We retrospectively gathered data from 428 patients who underwent percutaneous LAAO in 6 Italian high-volume centres, aimed at describing the real-world utilization, safety, and effectiveness of LAAO procedures, also assessing the clinical outcomes associated with different antithrombotic strategies. Results: Among the entire population, 20 (4.7 %) patients experienced a combination of pericardial effusion and periprocedural major bleeding: 8 (1.9 %) pericardial effusion, 1 (0.3 %) fatal bleeding, and 3 (0.7 %) non-fatal procedural major bleeding. Patients were discharged with different antithrombotic regimens: dual (DAPT) (27 %) or single (SAPT) (26 %) antiplatelet therapy, OAC (27 %), other antithrombotic regimens (14 %). Very few patients were not prescribed with antithrombotic drugs (6 %). At a medium 523 ± 58 days follow-up, 14 patients (3.3 %) experienced all-cause death, 6 patients (1.4 %) cardiovascular death, 3 patients (0.7 %) major bleeding, 10 patients (2.6 %) clinically relevant non-major bleeding, and 3 patients (0.7 %) ischemic stroke. At survival analysis, with DAPT as the reference group, OAC therapy was associated with better outcomes. Conclusions: Our findings confirm that LAAO is a safe procedure. Different individualized post-discharge antithrombotic regimens are now adopted, likely driven by the perceived thrombotic and hemorrhagic risk. The incidence of both ischemic and bleeding events tends to be low.

Ex Vivo Antiplatelet Effects of Oral Anticoagulants.

BACKGROUND: The impact of non-vitamin K antagonist oral anticoagulants (NOACs) on platelet function is still unclear. We conducted a comprehensive ex vivo study aimed at assessing the effect of the four currently marketed NOACs on platelet function. METHODS: We incubated blood samples from healthy donors with concentrations of NOACs (50, 150 and 250 ng/mL), in the range of those achieved in the plasma of patients during therapy. We evaluated generation of thrombin; light transmittance platelet aggregation (LTA) in response to adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), human γ-thrombin (THR) and tissue factor (TF); generation of thromboxane (TX)B2; and expression of protease-activated receptor (PAR)-1 and P-selectin on the platelet surface. RESULTS: All NOACs concentration-dependently reduced thrombin generation compared with control. THR-induced LTA was suppressed by the addition of dabigatran at any concentration, while TF-induced LTA was reduced by factor-Xa inhibitors. ADP- and TRAP-induced LTA was not modified by NOACs. TXB2 generation was reduced by all NOACs, particularly at the highest concentrations. We found a concentration-dependent increase in PAR-1 expression after incubation with dabigatran, mainly at the highest concentrations, but not with FXa inhibitors; P-selectin expression was not changed by any drugs. CONCLUSIONS: Treatment with the NOACs is associated with measurable ex vivo changes in platelet function, arguing for antiplatelet effects beyond the well-known anticoagulant activities of these drugs. There are differences, however, among the NOACs, especially between dabigatran and the FXa inhibitors.

Left Atrial Strain to Predict Postoperative Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery being associated with poorer outcomes. Revealing before the operation of left atrial subtle structural/functional abnormalities may help to identify patients at increased risk of POAF. We investigated the role of left atrial strain parameters by preoperative speckle tracking echocardiography as independent predictors of POAF in patients undergoing coronary artery bypass graft. METHODS: Consecutive patients undergoing isolated coronary artery bypass graft were prospectively enrolled at three Italian centers. All patients underwent transthoracic echocardiography before the operation. The occurrence of POAF up to discharge was monitored. RESULTS: Overall, a total of 310 patients were included. POAF was demonstrated in 103 patients (33%). At receiver operating characteristic curve analysis, lower global peak atrial longitudinal strain (PALS) values significantly predicted the risk of POAF (area under the curve, 0.74; P<0.001). The optimal cutoff value for the arrhythmia prediction was a global PALS value <28%, with a specificity of 86% and a sensitivity of 36%. The incidence of POAF was 51% in patients with global PALS <28% versus 14% in those with PALS ≥28% (P<0.001), with a POAF-free survival at Kaplan-Meier analysis of 45.4% and 85.7%, respectively (P<0.001). At multivariate analysis, a global PALS <28% carried a 3.6-fold higher risk of POAF (hazard ratio, 3.6 [95% CI, 2.2-5.9]; P<0.001). The risk increase was even higher when PALS <28% was associated with age ≥70 years (adjusted hazard ratio, 11.2 [4.7-26.6], P<0.001). CONCLUSIONS: A presurgery global PALS <28% is a specific parameter to stratify patients at increased risk of POAF after coronary artery bypass graft. This assessment can be useful to identify patients at higher arrhythmic risk in whom perioperative preventive strategies and stricter monitoring aimed at early diagnosing and treating POAF may be applied.

Revisiting Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Current Practice and Novel Perspectives.

Sarcomeric hypertrophic cardiomyopathy (HCM) is a prevalent genetic disorder characterised by left ventricular hypertrophy, myocardial disarray, and an increased risk of heart failure and sudden cardiac death. Despite advances in understanding its pathophysiology, treatment options for HCM remain limited. This narrative review aims to provide a comprehensive overview of current clinical practice and explore emerging therapeutic strategies for sarcomeric HCM, with a focus on cardiac myosin inhibitors. We first discuss the conventional management of HCM, including lifestyle modifications, pharmacological therapies, and invasive interventions, emphasizing their limitations and challenges. Next, we highlight recent advances in molecular genetics and their potential applications in refining HCM diagnosis, risk stratification, and treatment. We delve into emerging therapies, such as gene editing, RNA-based therapies, targeted small molecules, and cardiac myosin modulators like mavacamten and aficamten, which hold promise in modulating the underlying molecular mechanisms of HCM. Mavacamten and aficamten, selective modulators of cardiac myosin, have demonstrated encouraging results in clinical trials by reducing left ventricular outflow tract obstruction and improving symptoms in patients with obstructive HCM. We discuss their mechanisms of action, clinical trial outcomes, and potential implications for the future of HCM management. Furthermore, we examine the role of precision medicine in HCM management, exploring how individualised treatment strategies, including exercise prescription as part of the management plan, may optimise patient outcomes. Finally, we underscore the importance of multidisciplinary care and patient-centred approaches to address the complex needs of HCM patients. This review also aims to encourage further research and collaboration in the field of HCM, promoting the development of novel and more effective therapeutic strategies, such as cardiac myosin modulators, to hopefully improve the quality of life and outcome of patients with sarcomeric HCM.

Sex Differences in Heart Failure: What Do We Know?

Heart failure (HF) remains an important global health issue, substantially contributing to morbidity and mortality. According to epidemiological studies, men and women face nearly equivalent lifetime risks for HF. However, their experiences diverge significantly when it comes to HF subtypes: men tend to develop HF with reduced ejection fraction more frequently, whereas women are predominantly affected by HF with preserved ejection fraction. This divergence underlines the presence of numerous sex-based disparities across various facets of HF, encompassing aspects such as risk factors, clinical presentation, underlying pathophysiology, and response to therapy. Despite these apparent discrepancies, our understanding of them is far from complete, with key knowledge gaps still existing. Current guidelines from various professional societies acknowledge the existence of sex-based differences in HF management, yet they are lacking in providing explicit, actionable recommendations tailored to these differences. In this comprehensive review, we delve deeper into these sex-specific differences within the context of HF, critically examining associated definitions, risk factors, and therapeutic strategies. We provide a specific emphasis on aspects exclusive to women, such as the impact of pregnancy-induced hypertension and premature menopause, as these unique factors warrant greater attention in the broader HF discussion. Additionally, we aim to clarify ongoing controversies and knowledge gaps pertaining to the pharmacological treatment of HF and the sex-specific indications for cardiac implantable electronic devices. By shining a light on these issues, we hope to stimulate a more nuanced understanding and promote the development of more sex-responsive approaches in HF management.

The Impact of Physical Activity and Inactivity on Cardiovascular Risk across Women's Lifespan: An Updated Review.

Physical inactivity (PI) represents a significant, modifiable risk factor that is more frequent and severe in the female population worldwide for all age groups. The physical activity (PA) gender gap begins early in life and leads to considerable short-term and long-term adverse effects on health outcomes, especially cardiovascular (CV) health. Our review aims to highlight the prevalence and mechanisms of PI across women's lifespan, describing the beneficial effects of PA in many physiological and pathological clinical scenarios and underlining the need for more awareness and global commitment to promote strategies to bridge the PA gender gap and limit PI in current and future female generations.

Cardiovascular Morbidity and Mortality Related to Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

Whether non-alcoholic fatty liver disease (NAFLD) is a cardiovascular (CV) risk factor is debated. We performed a systematic review and meta-analysis to assess the CV morbidity and mortality related to NAFLD in the general population, and to determine whether CV risk is comparable between lean and non-lean NAFLD phenotypes. We searched multiple databases, including PubMed, Embase, and the Cochrane Library, for observational studies published through 2022 that reported the risk of CV events and mortality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for all-cause mortality, CV mortality, myocardial infarction (MI), stroke, atrial fibrillation (AF), and major adverse cardiovascular and cerebrovascular events (MACCE) were assessed through random-effect meta-analysis. We identified 33 studies and a total study population of 10,592,851 individuals (mean age 53±8; male sex 50%; NAFLD 2, 9%). Mean follow-up was 10±6 years. Pooled ORs for all-cause and CV mortality were respectively 1.14 (95% CI, 0.78-1.67) and 1.13 (95% CI, 0.57-2.23), indicating no significant association between NAFLD and mortality. NAFLD was associated with increased risk of MI (OR 1.6; 95% CI, 1.5-1.7), stroke (OR: 1.6; 95% CI, 1.2-2.1), atrial fibrillation (OR: 1.7; 95% CI, 1.2-2.3), and MACCE (OR: 2.3; 95% CI, 1.3-4.2). Compared with non-lean NAFLD, lean NAFLD was associated with increased CV mortality (OR: 1.50; 95% CI, 1.1-2.0), but similar all-cause mortality and risk of MACCE. While NAFLD may not be a risk factor for total and CV mortality, it is associated with excess risk of non-fatal CV events. Lean and non-lean NAFLD phenotypes exhibit distinct prognostic profiles and should receive equitable clinical care.

Monitoring antiplatelet therapy: where are we now?

Single antiplatelet therapy represents the cornerstone of thrombosis prevention in atherosclerotic cardiovascular disease. Dual antiplatelet therapy (DAPT), consisting of aspirin plus a P2Y 12 inhibitor, is the standard of care for patients with acute coronary syndrome or undergoing both coronary and peripheral percutaneous interventions. Recent data suggest the efficacy of DAPT also after minor stroke. In this setting, a large body of evidence has documented that genetic and acquired patients' characteristics may affect the magnitude of platelet inhibition induced by antiplatelet agents. The implementation of tools allowing the identification and prediction of platelet inhibition has recently been shown to improve outcomes, leading to an optimal balance between antithrombotic efficacy and bleeding risk. We are therefore clearly moving towards tailored antiplatelet therapy. The aim of this paper is to summarize the available evidence on the evaluation of platelet inhibition in patients with coronary, peripheral, or cerebrovascular atherosclerosis. We will here focus on antiplatelet therapy based on both aspirin and P2Y 12 inhibitors. In addition, we provide practical insights into the clinical settings in which it appears reasonable to implement antiplatelet therapy monitoring.

Predictive Value of Echocardiographic Pulmonary to Left Atrial Ratio for In-Hospital Death in Patients with COVID-19.

Background: Echocardiographic Pulmonary to Left Atrial Ratio (ePLAR) represents an accurate and sensitive non-invasive tool to estimate the trans-pulmonary gradient. The prognostic value of ePLAR in hospitalized patients with COVID-19 remains unknown. We aimed to investigate the predictive value of ePLAR on in-hospital mortality in patients with COVID-19. Methods: One hundred consecutive patients admitted to two Italian institutions for COVID-19 undergoing early (<24 h) echocardiographic examination were included; ePLAR was determined from the maximum tricuspid regurgitation continuous wave Doppler velocity (m/s) divided by the transmitral E-wave: septal mitral annular Doppler Tissue Imaging e'-wave ratio (TRVmax/E:e'). The primary outcome measure was in-hospital death. Results: patients who died during hospitalization had at baseline a higher prevalence of tricuspid regurgitation, higher ePLAR, right-side pressures, lower Tricuspid Annular Plane Systolic Excursion (TAPSE)/ systolic Pulmonary Artery Pressure (sPAP) ratio and reduced inferior vena cava collapse than survivors. Patients with ePLAR > 0.28 m/s at baseline showed non-significant but markedly increased in-hospital mortality compared to those having ePLAR ≤ 0.28 m/s (27% vs. 10.8%, p = 0.055). Multivariate Cox regression showed that an ePLAR > 0.28 m/s was independently associated with an increased risk of death (HR 5.07, 95% CI 1.04−24.50, p = 0.043), particularly when associated with increased sPAP (p for interaction = 0.043). Conclusions: A high ePLAR value at baseline predicts in-hospital death in patients with COVID-19, especially in those with elevated pulmonary arterial pressure. These results support an early ePLAR assessment in patients admitted for COVID-19 to identify those at higher risk and potentially guide strategies of diagnosis and care.

Prediction of Masked Uncontrolled Hypertension Detected by Ambulatory Blood Pressure Monitoring.

The aim of this study was to provide prediction models for masked uncontrolled hypertension (MUCH) detected by ambulatory blood pressure (BP) monitoring in an Italian population. We studied 738 treated hypertensive patients with normal clinic BPs classified as having controlled hypertension (CH) or MUCH if their daytime BP was < or ≥135/85 mmHg regardless of nighttime BP, respectively, or CH or MUCH if their 24-h BP was < or ≥130/80 mmHg regardless of daytime or nighttime BP, respectively. We detected 215 (29%) and 275 (37%) patients with MUCH using daytime and 24-h BP thresholds, respectively. Multivariate logistic regression analysis showed that males, those with a smoking habit, left ventricular hypertrophy (LVH), and a clinic systolic BP between 130−139 mmHg and/or clinic diastolic BP between 85−89 mmHg were associated with MUCH. The area under the receiver operating characteristic curve showed good accuracy at 0.78 (95% CI 0.75−0.81, p < 0.0001) and 0.77 (95% CI 0.73−0.80, p < 0.0001) for MUCH defined by daytime and 24 h BP, respectively. Internal validation suggested a good predictive performance of the models. Males, those with a smoking habit, LVH, and high-normal clinic BP are indicators of MUCH and models including these factors provide good diagnostic accuracy in identifying this ambulatory BP phenotype.

Design of the PERSEO Registry on the management of patients treated with oral anticoagulants and coronary stent.

AIM: Percutaneous coronary intervention with stent implantation (PCI-S) in patients requiring chronic oral anticoagulant therapy (OAC) is associated with an increased risk of bleeding and ischemic complications. Different randomized studies showed a significant advantage of a double antithrombotic therapy and superiority of direct oral anticoagulant (DOAC) compared with warfarin, but real-world data are limited. Aim is to evaluate the antithrombotic management and clinical outcome of patients with an indication for OAC who undergo PCI-S in a 'real-world' setting. METHODS: The multicentre prospective observational PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) Registry (ClinicalTrials.gov Identifier: NCT03392948) has been designed to enrol patients requiring OAC treated by PCI-S in 25 Italian centres. A target of at least 1080 patients will be followed for 1 year and data on thromboembolic and bleeding events and changes in antithrombotic therapy will be registered. The primary end point is a combined measure of efficacy and safety outcome (NACE), including major bleeding events and major adverse cardiac and cerebral events at 1-year follow-up in patients treated with DOAC (and dual or triple antiplatelet therapy) compared with the corresponding strategies with vitamin K antagonists. A secondary prespecified analysis has been defined to evaluate NACE in dual versus triple antithrombotic therapy after hospital discharge at 1-year follow-up. CONCLUSION: The PERSEO Registry will investigate in a 'real world' setting the safety and efficacy of DOAC versus warfarin and dual versus triple antithrombotic therapy in patients with indication for oral anticoagulant therapy who undergo PCI-S.

Urine alkalinisation to prevent contrast-induced acute kidney injury: the prospective, randomised, controlled, open-label TEATE trial.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is prognostically relevant in invasive cardiological and radiological procedures. The administration of sodium bicarbonate has controversial effects. It has been hypothesised that bicarbonate is ineffective when unable to achieve adequate urine alkalinisation. AIMS: We tested the hypothesis that alkaline urine status with oral or intravenous (i.v.) bicarbonate on top of hydration alone prevents CI-AKI. METHODS: In a prospective, randomised, parallel-group, open-label trial, we compared 1) saline hydration alone (n=81); 2) i.v. bicarbonate (n=82); and 3) oral bicarbonate (n=78), in patients with chronic kidney disease (CKD) scheduled for the intra-arterial administration of contrast medium. The primary endpoint was the incidence of CI-AKI according to alkaline urine status achieved immediately before angiography. Secondary endpoints were the mean change of urine pH up to the time of angiography and the incidence of CI-AKI in the three groups. RESULTS: The incidence of CI-AKI was not significantly different in the three treatment arms (20% in the hydration group, 21% in the oral bicarbonate group and 22% in the i.v. bicarbonate group; p=0.94). Patients achieving a pH >6 before angiography (n=145) had a significantly lower incidence of CI-AKI compared with the others (n=96; odds ratio [OR] 0.48, 95% confidence interval [CI]: 0.25-0.90; p=0.023, primary study hypothesis). The proportion of patients achieving a pH >6 was higher in the i.v. and oral bicarbonate groups compared with hydration alone. CONCLUSIONS: Urinary pH before administration of contrast medium is an inverse correlate of CI-AKI incidence, and bicarbonate is superior to hydration alone in achieving urinary alkalinisation. Since, however, bicarbonate did not reduce the incidence of CI-AKI, we conclude that urinary pH is a marker and not a mediator of CI-AKI (ClinicalTrials.gov: NCT02980003).

Predictive Value of Left Atrial and Ventricular Strain for the Detection of Atrial Fibrillation in Patients With Cryptogenic Stroke.

Background and Aims: Cryptogenic stroke (CS) is associated with a high rate of recurrences and adverse outcomes at long-term follow-up, especially due to its unknown etiology that often leads to ineffective secondary prevention. Asymptomatic atrial fibrillation (AF) could play an important pathophysiological role. Some studies have pointed to left atrial (LA) and left ventricular (LV) systolic and diastolic dysfunction as surrogate markers of AF. The aim of the study is to evaluate the relationship between echocardiographic parameters of LA and LV function, and the occurrence of AF revealed by continuous ECG monitoring in a cohort of patients with CS. Methods: Single-center prospective cohort study. Seventy-two patients with CS with insertable cardiac monitors (ICM) underwent transthoracic echocardiography (TTE). TTE was focused on LA and LV function, including both standard and longitudinal strain-derived parameters. All detected AF episodes lasting more than 2 min were considered. Results: Continuous ECG monitoring revealed subclinical AF in 23 patients (32%) at an average of 6.5 months after ICM implantation. Many echocardiographic parameters, indicating LA volume and LV systolic/diastolic function, were significantly associated with the occurrence of AF, suggesting the worst atrial function in the AF group. Furthermore, multivariable regression analysis revealed that peak atrial contraction strain and left ventricular strain were independently associated with AF (adjusted OR = 0.72, CI 95% 0.48-0.90, p = 0.005, and adjusted OR = 0.69, CI 95% 0.46-0.95, p = 0.041, respectively). Conclusion: In patients with CS, LA and LV strain analysis add predictive value for the occurrence of AF over clinical and morpho-functional echocardiographic parameters. Impaired booster pump strain and LV longitudinal strain are strong and independent predictors of AF.

A Prospective Study to Evaluate the Effectiveness of Edoxaban for the Resolution of Left Atrial Thrombosis in Patients with Atrial Fibrillation.

Available evidence on left atrial (LA) thrombus dissolution in patients with atrial fibrillation (AF) largely refers to the use of vitamin K antagonist oral anticoagulants (VKAs), showing >50% thrombus resolution over a 4-week to 12-month treatment period. Available data on non-vitamin K antagonist anticoagulants (NOACs) in this setting are limited and derive from isolated case reports or observational small-sized investigations with dabigatran, rivaroxaban or apixaban. The aim of this study was to investigate the extent of thrombus resolution with edoxaban therapy in patients with AF and LA thrombosis. We conducted a prospective, observational, open-label pilot study in seven Italian institutions. We included a total of 25 patients with non-valvular AF and LA (or left atrial appendage (LAA)) thrombosis, documented by transesophageal echocardiography (TEE). All patients received edoxaban OD treatment (n = 23 on 60 mg daily; n = 2 on 30 mg daily) and underwent TEE examination after 4 weeks. The primary endpoint was the percentage of patients with complete thrombus resolution by TEE imaging at 4 weeks. The mean age of the study population was 68.3 ± 10.8 years with a female population of 16%. AF was permanent in all cases, with a mean arrhythmia duration of 4.3 ± 1.7 years. CHA2DS2-VASc and HAS-BLED scores were 3.2 ± 1.5 and 1.9 ± 1.1, respectively. We were able to demonstrate a complete thrombus resolution in 14 patients (56%) at 4 weeks. In patients with residual atrial thrombosis (n = 11), we observed a 15.4 ± 14.9% reduction in the thrombus area from baseline. As compared with patients without thrombus dissolution, those with thrombus resolution had a numerically lower-indexed LA diameter (27.9 ± 9.3 vs 34.8 ± 16.1 mm/m2), a smaller maximum thrombus area at baseline (45.5 ± 44.6 vs 63.9 ± 43.5 mm2), a higher left ventricular ejection fraction (47.4 ± 21.0% vs 38.4 ± 20.6%) and higher maximum LAA flow velocities (26.3 ± 15.2 vs 19.3 ± 10.0 cm/s). Figures on the percentage of thrombus resolution in this study are comparable to those reported in the literature for the other OACs. We conclude that, in patients with AF, the use of edoxaban is associated with a >50% resolution of atrial thrombus at 4 weeks, similar to studies using VKAs and the other NOACs (ClinicalTrials.gov identifier number: NCT034899395).

Prognostic value of non-resistant and resistant masked uncontrolled hypertension detected by ambulatory blood pressure monitoring.

Masked uncontrolled hypertension (MUCH) is at higher cardiovascular risk than controlled hypertension (CH). In previous studies, patients with MUCH were considered as a unique group though those receiving ≤2 drugs could be defined as having nonresistant MUCH (NRMUCH) and those receiving ≥3 drugs as having resistant MUCH (RMUCH). The aim of this study was to assess the prognostic value of NRMUCH and RMUCH detected by ambulatory blood pressure (BP) monitoring. Cardiovascular risk was evaluated in 738 treated hypertensive patients with normal clinic BP. Patients were classified as having CH or MUCH if daytime BP < or ≥ 135/85 mmHg, respectively, regardless of nighttime BP, or CH or MUCH if 24-h BP < or ≥ 130/80 mmHg, respectively, regardless of daytime or nighttime BP. By daytime or 24-h BP, the authors detected 523 (71%), 178 (24%), and 37 (5%) or 463 (63%), 231 (31%), and 44 (6%) patients with CH, NRMUCH, and RMUCH, respectively. During the follow-up (median 10 years), 148 events occurred. After adjustment for covariates, compared to CH, the hazard ratio (HR), 95% confidence interval (CI), for cardiovascular events was 1.81, 1.27-2.57, and 2.99, 1.73-5.16, in NRMUCH and RMUCH defined by daytime BP, respectively, and 1.58, 1.12-2.23, and 2.21, 1.27-3.82, in NRMUCH and RMUCH defined by 24-h BP, respectively. If RMUCH was compared with NRMUCH, the risk tended to be higher in RMUCH but did not attain statistical significance (P = .08 and P = .23 by daytime and 24-h BP thresholds, respectively). In conclusion, both NRMUCH and RMUCH are at increased cardiovascular risk than CH.