Left atrial appendage closure for stroke prevention in atrial fibrillation: current status and perspectives.

Atrial fibrillation (AF) is associated with an increased risk of stroke and systemic embolism, and the left atrial appendage (LAA) has been identified as a principal source of thromboembolism in these patients. While oral anticoagulation is the current standard of care, LAA closure (LAAC) emerges as an alternative or complementary treatment approach to reduce the risk of stroke or systemic embolism in patients with AF. Moderate-sized randomized clinical studies have provided data for the efficacy and safety of catheter-based LAAC, largely compared with vitamin K antagonists. LAA device iterations, advances in pre- and peri-procedural imaging, and implantation techniques continue to increase the efficacy and safety of LAAC. More data about efficacy and safety of LAAC have been collected, and several randomized clinical trials are currently underway to compare LAAC with best medical care (including non-vitamin K antagonist oral anticoagulants) in different clinical settings. Surgical LAAC in patients with AF undergoing cardiac surgery reduced the risk of stroke on background of anticoagulation therapy in the LAAOS III study. In this review, we describe the rapidly evolving field of LAAC and discuss recent clinical data, ongoing studies, open questions, and current limitations of LAAC.

Sex-Related Differences in Clinical Outcomes in Patients with Atrial Fibrillation and Coronary Artery Disease: A Sub-Study of the MISOAC-AF Randomized Controlled Trial.

BACKGROUND: There is limited "real-world" data on the prognostic role of gender in comorbid atrial fibrillation (AF) and coronary artery disease (CAD). METHODS: In this post-hoc analysis of the MISOAC-AF randomized trial (NCT: 02941978), consecutive patients with AF and CAD who were discharged from the cardiology ward between 2015 and 2018 were included. Multivariable Cox-regression analysis was performed for all-cause mortality and cardiovascular (CV) mortality. Competing-risk analysis was performed for the outcomes of stroke or systemic embolism, major bleeding, AF- or heart failure (HF)-related hospitalization, adjusted for the competing risk of all-cause death. RESULTS: Of 1098 patients with AF, 461 patients with comorbid CAD were analyzed. Women were older and more likely to have a history of diabetes mellitus and valvular heart disease, while men were more likely to have a history of smoking or myocardial infarction. Over a median follow-up of 31 months, 143 (43.4%) men and 71 (53.7%) women died. Women were at a higher risk for all-cause mortality (adjusted hazard ration [aHR] 1.65; 95% confidence interval [CI] 1.14-2.38) and stroke or systemic embolism (aHR 3.52; 95% CI 1.46-8.49) compared to men. The risks of CV mortality, major bleeding, AF-related hospitalization, and HF-related hospitalization were similar between genders. CONCLUSIONS: In recently hospitalized patients with AF and comorbid CAD, the female gender was independently associated with increased all-cause mortality and thromboembolic events.

Polypharmacy and Major Adverse Events in Atrial Fibrillation.

ABSTRACT: Patients with atrial fibrillation (AF) often receive multiple medications daily. The purpose of this study was to examine the prognostic implications of polypharmacy in patients with AF. This is a retrospective post hoc analysis of 1113 AF patients, enrolled in a randomized trial during an acute hospitalization (MISOAC-AF, NCT02941978). The presence of polypharmacy (use of >4 drugs daily) was assessed at hospital discharge. Regression analyses were performed to identify clinical predictors of polypharmacy and compare the outcomes of patients with or without confirmed polypharmacy. The coprimary outcomes were all-cause and cardiovascular (CV) mortality. Among patients with polypharmacy, the difference in the risk of mortality was also assessed per each added drug as a numeric variable. Polypharmacy was found in 36.9% of participants. Dyslipidemia, coronary artery disease, lower left ventricular ejection fraction, and higher glomerular filtration rates were independent predictors of polypharmacy. Polypharmacy was an independent predictor for all-cause death (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI]: 1.01-1.64) and CV death (aHR: 1.39, 95% CI: 1.05-1.84). Among patients with polypharmacy, each additional concomitant medication was independently associated with a 4% increased risk of all-cause mortality (aHR = 1.04, 95% CI: 1.00-1.08) and a 5% increased risk of CV mortality (aHR = 1.05, 95% CI: 1.00-1.10). Polypharmacy was common among patients with AF hospitalized in a tertiary hospital and was incrementally associated with higher rates of mortality.

Risk for Recurrent Cardiovascular Events and Expected Risk Reduction With Optimal Treatment 1 Year After an Acute Coronary Syndrome.

According to the latest European Society of Cardiology Guidelines for the diagnosis and management of chronic coronary syndromes, patients who suffered an acute coronary syndrome fall into a chronic stable phase after 1 year. In these patients, the estimated 10-year risk for recurrent cardiovascular events varies considerably. We applied the SMART (Second Manifestations of Arterial Disease) risk score in 281 patients 1 year after an acute coronary syndrome to estimate the 10-year risk for recurrent cardiovascular events (subsequent nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). We assessed the distribution of the estimated risk and the potential risk reduction that might be achieved with optimal guideline-directed management of modifiable risk factors (systolic blood pressure, low-density lipoprotein cholesterol, smoking, and body mass index). In our cohort, the median SMART score was 16.1% (interquartile range [IQR] 9.7 to 27.3), particularly increased in patients with older age, diabetes, polyvascular disease or chronic kidney disease (median 28.6%, IQR 20.8 to 52.9; 23.8%, 4.8 to 41.6; 29.4%, 18.8 to 49.7; 53.8%, 26.5 to 71.6, respectively). If all modifiable risk factors met guideline-recommended targets, the median SMART risk score would be 9.6% (IQR 6.3 to 20.9), with 51% of the patients at a 10-year risk <10%, while 11% and 15% at 20% to 30% and >30% risk, respectively. In conclusion, the SMART score had a wide distribution in patients with chronic coronary syndromes. A quarter of patients remained at a >20% 10-year risk, even with optimal risk factor management, clearly underlining that residual risk is an unmet clinical challenge.

Flaws in Anticoagulation Strategies in Patients With Atrial Fibrillation at Hospital Discharge.

BACKGROUND: Proper anticoagulation is a crucial therapeutic regimen in atrial fibrillation (AF). OBJECTIVES: To evaluate the real-life anticoagulation prescriptions of AF patients upon hospital discharge. METHODS: We studied 768 patients with comorbid AF who were discharged from the cardiology ward of a tertiary hospital. We assessed the appropriateness of oral anticoagulation (OAC) regimens at discharge based on stroke risk (CHA2DS2-Vasc score), SAMe-TT2R2 (sex, age, medical history, treatment, tobacco, race) score for vitamin K antagonists (VKA), and European labeling for nonvitamin K oral anticoagulant (NOAC) dosing. Logistic regression identified factors associated with suboptimal OAC use. RESULTS: Of 734 patients at significant (moderate or high) stroke risk, 107 (14.6%) were not prescribed OAC, which was administered to 23 (67.6%) of 34 patients at low risk. Nonprescribing of OAC to high-risk patients was associated with paroxysmal AF (adjusted odds ratio [OR]: 2.42, 95% confidence interval [CI]: 1.47-3.99, P < .001), history of major bleeding (adjusted OR: 1.89, 95% CI: 1.03-3.47, P = .039), and concomitant antiplatelet use (adjusted OR: 5.78, 95% CI: 3.51-9.51, P < .001). Anticoagulation control was inadequate (SAMe-TT2R2 score > 2) in 102 (50.2%) VKA-treated patients. Off-label dosing was evident in 118 (28.9%) NOAC-treated patients and was associated with a prior stroke/transient ischemic attack (adjusted OR: 2.06, 95% CI: 1.10-3.85, P = .023). Both outcomes were independently associated with low creatinine clearance. CONCLUSIONS: One of 6 patients with AF newly discharged from the hospital was treated discordantly for the corresponding risk of stroke. Suboptimal OAC use was evident in half of VKA regimens, twice as common compared to NOACs, and could be predicted by several clinical parameters.

Incidence and Clinical Impact of Device-Associated Thrombus and Peri-Device Leak Following Left Atrial Appendage Closure With the Amplatzer Cardiac Plug.

OBJECTIVES: Routine device surveillance after successful left atrial appendage closure is recommended to evaluate for intermediate to late complications. The aim of this study was to assess the incidence and clinical impact of these complications on cardiovascular events. METHODS: Centers participating in the Amplatzer Cardiac Plug multicenter study were requested to submit their post-procedural transesophageal echocardiograms for independent adjudication. Thirteen of 22 centers contributed all their post-procedural echocardiograms, which included 344 from 605 consecutive patients. These images were submitted to a core laboratory and reviewed by 2 independent experts for peri-device leak, device-associated thrombus, device embolization, device migration, left atrial appendage thrombus, and left atrial thrombus. Clinical events were prospectively collected by each center. RESULTS: Of the 344 transesophageal echocardiograms, 339 were deemed analyzable. Patients' mean age was 74.4 ± 7.5 years, and 67.3% were men. The mean CHADS2 score was 2.7 ± 1.3, the mean CHA2DS2-VASc score was 4.3 ± 1.5, and the mean HAS-BLED score was 3.0 ± 1.2. Amplatzer Cardiac Plug implantation was successful in all patients. Periprocedural major adverse events occurred in 2.4%. Median clinical follow-up duration was 355 days (range 179 to 622 days). Follow-up transesophageal echocardiography was performed after a median of 134 days (range 88 to 227 days). Device-associated thrombus was observed in 3.2% and peri-device leak in 12.5% (5.5% minimal, 5.8% mild, 0.6% moderate, 0.6% severe). Neither device-associated thrombus nor peri-device leak was associated with an increased risk for cardiovascular events. Independent predictors of device-associated thrombus were smoking (odds ratio: 5.79; p = 0.017) and female sex (odds ratio: 4.22; p = 0.027). CONCLUSIONS: Following successful left atrial appendage closure with the Amplatzer Cardiac Plug, the presence of peri-device leak was relatively low, and device-associated thrombus was infrequent. Neither was associated with increased risk for thromboembolism.

Novel nonpharmacologic approaches for stroke prevention in atrial fibrillation: results from clinical trials.

Atrial fibrillation (AF), the most common cardiac arrhythmia, confers a 5-fold risk of stroke that increases to 17-fold when associated with mitral stenosis. At this time, the most effective long-term solution to protect patients from stroke and thromboembolism is oral anticoagulation, either with vitamin K antagonists (VKAs) or a novel oral anticoagulant (NOAC). Despite the significant benefits they confer, both VKAs and NOACs are underused because of their increased potential for bleeding, and VKAs are underused because of their narrow therapeutic range, need for regular international normalized ratio checks, and interactions with food or medications. In patients with nonvalvular AF, approximately 90% of strokes originate from the left atrial appendage (LAA); in patients with rheumatic mitral valve disease, many patients (60%) have strokes that originate from the left atrium itself. Surgical LAA amputation or closure, although widely used to reduce stroke risk in association with cardiac surgery, is not currently performed as a stand-alone operation for stroke risk reduction because of its invasiveness. Percutaneous LAA closure, as an alternative to anticoagulation, has been increasingly used during the last decade in an effort to reduce stroke risk in nonvalvular AF. Several devices have been introduced during this time, of which one has demonstrated noninferiority compared with warfarin in a randomized controlled trial. This review describes the available technologies for percutaneous LAA closure, as well as a summary of the published trials concerning their safety and efficacy in reducing stroke risk in AF.

Intra-procedural imaging of the left atrial appendage: implications for closure with the Amplatzer™ cardiac plug.

OBJECTIVES: To evaluate intra-procedural imaging with transesophageal echocardiography and angiography during left atrial appendage occlusion using the Amplatzer™ Cardiac Plug with regard to sizing and final device shape. METHODS: Left atrial appendage ostium dimensions and diameter at a depth of 10mm from the ostium were measured by transesophageal echocardiography (0-180°) and angiography (RAO 30° - Cranial 20°) in consecutive patients undergoing left atrial appendage occlusion using the ACP with an oversizing strategy of 10-20% relative to the baseline measurements. After delivery, ACP dimensions were measured and device shape was assessed. RESULTS: Twenty-seven consecutive patients underwent successful uncomplicated left atrial appendage closure with Amplatzer™ Cardiac Plug. We found a significant difference between the largest and smallest left atrial appendage diameter measured with transesophageal echocardiography (22.3±4.2 vs. 18.1±4.1mm, p<0.001). By the end of the procedure (by angiography), ACP had an optimal shape in 17 patients (63%), a strawberry-like shape in 7 patients (26%), and a square-like shape in 3 patients (11%). ACP was oversized on average by 1.5±2.7 and 3.3±2.3mm compared to transesophageal echocardiography and angiography, respectively. The final shape of the device was not significantly associated with the degree of oversizing. CONCLUSIONS: We found a considerable variability in the assessment of the left atrial appendage, using transesophageal echocardiography and angiography. The degree of Amplatzer™ Cardiac Plug expansion within the left atrial appendage and the final shape of the device were not associated with the degree of oversizing.

Intra-procedural imaging of the left atrial appendage: Implications for closure with the AmplatzerTM cardiac plug / Evaluación de la orejuela izquierda durante el cierre percutáneo con el dispositivo AmplatzerTM cardiac plug

Objectives: To evaluate intra-procedural imaging with transesophageal echocardiography and angiography during left atrial appendage occlusion using the Amplatzer™ Cardiac Plug with regard to sizing and final device shape. Methods: Left atrial appendage ostium dimensions and diameter at a depth of 10 mm from the ostium were measured by transesophageal echocardiography (0-180°) and angiography (RAO 30° - Cranial 20°) in consecutive patients undergoing left atrial appendage occlusion using the ACP with an oversizing strategy of 10-20% relative to the baseline measurements. After delivery, ACP dimensions were measured and device shape was assessed. Results: Twenty-seven consecutive patients underwent successful uncomplicated left atrial appendage closure with Amplatzer™ Cardiac Plug. We found a significant difference between the largest and smallest left atrial appendage diameter measured with transesophageal echocardiography (22.3 ± 4.2 vs. 18.1 ± 4.1 mm, p <0.001). By the end of the procedure (by angiography), ACP had an optimal shape in 17 patients (63%), a strawberry-like shape in 7 patients (26%), and a square-like shape in 3 patients (11%). ACP was oversized on average by 1.5±2.7 and 3.3±2.3mm compared to transesophageal echocardiography and angiography, respectively. The final shape of the device was not significantly associated with the degree of oversizing. Conclusions: We found a considerable variability in the assessment of the left atrial appendage, using transesophageal echocardiography and angiography. The degree of Amplatzer™ Cardiac Plug expansion within the left atrial appendage and the final shape of the device were not associated with the degree of oversizing.

Objetivos: Evaluar las dimensiones de la orejuela izquierda antes del cierre percutáneo y la correlación de sus dimensiones finales y la forma del dispositivo Amplatzer™ cardiac plug con ecocardiografia transesofágica y angiografia. Métodos: Se midieron las dimensiones de la orejuela izquierda a una distancia de 10 mm a partir del ostium con ecocardiografia transesofágica (0 a 180°) y angiografia (RAO 30° Craneal 20°). Se utilizó una estrategia para sobre dimensionar el tamano del dispositivo del 10 al 20% con respecto a las mediciones iniciales. Se evaluaron las dimensiones y la forma final del dispositivo. Resultados: Se realizó el procedimiento en 27 pacientes. Se encontró una diferencia significativa entre el diámetro mayor y menor de orejuela izquierda medido por ecocardiografia transesofágica (22.3±4.2 vs 18.1 ±4.1 mm, p< 0.001). Una vez liberado el dispositivo, se encontró que en 17 pacientes (63%) adoptó una forma óptima, de "fresa" en 7 (26%) y cuadrada en 3 (11%). El tamaño del dispositivo seleccionado se sobre dimensionó en promedio 1.5 ± 2.7mm con la ecocardiografia transesofágica y 3.3 ± 2.3 mm con la angiografia. La forma final del dispositivo no se asoció de manera significativa con el grado de sobre dimensionamiento del mismo. Conclusiones: Existe variabilidad considerable en la evaluación de la orejuela izquierda entre la ecocardiografia transesofágica y la angiografia. No se encontró asociación entre el grado de expansión del dispositivo dentro de la orejuela izquierda ni de su forma final con el grado de sobre dimensionamiento del mismo.

Left ventricular mass regression one year after transcatheter aortic valve implantation.

BACKGROUND: Left ventricular (LV) hypertrophy is associated with LV diastolic dysfunction and constitutes a risk factor for cardiac morbidity and mortality. The objective of this study was to investigate the degree of LV mass regression and the changes of LV diastolic function one year after transcatheter aortic valve implantation (TAVI). METHODS: Echocardiography was performed at baseline, before discharge, and at one-year follow-up in 63 consecutive patients with severe aortic stenosis who underwent TAVI with the Medtronic CoreValve System (Medtronic Inc, Minneapolis, MN). The LV mass was calculated using the Devereux formula and indexed to body surface area. RESULTS: One-year all-cause mortality was 29%. The LV mass index decreased from 126 ± 42 g/m(2) at baseline to 110 ± 30 g/m(2) at one-year follow-up (p < 0.001). Left ventricular ejection fraction and LV diastolic function did not change significantly. Mean transaortic gradient decreased from 47 ± 19 mm Hg at baseline to 9 ± 5 mm Hg at discharge and 9 ± 4 mm Hg at one year (p < 0.001), and was accompanied by significant clinical improvement. More than mild paravalvular aortic regurgitation was found in 24% and 15% of patients at discharge and one-year follow-up, respectively. CONCLUSIONS: A significant regression in LV mass was found one year after TAVI. However, regression was incomplete and was not accompanied by an improvement in LV diastolic function.

How should I treat a staggering TAVI procedure?

BACKGROUND: A 79-year-old female patient with past medical history of chronic myeloid leukaemia, presented to the outpatient cardiology clinic with shortness of breath (NYHA class 3) and fatigue. INVESTIGATION: Echocardiography (ECG) and multislice computed tomography (MSCT). DIAGNOSIS: Severe calcified aortic valve stenosis by echocardiography. Logistic EuroSCORE 10.3. Porcelain aorta by multislice computed tomography (MSCT). TREATMENT: Transcatheter aortic valve implantation (TAVI) with an 18 Fr Medtronic-CoreValve system (Medtronic Inc., Minneapolis, MN, USA) using a right transfemoral arterial approach.