Persistent and Recurrent Device-Related Thrombus After Left Atrial Appendage Closure: Incidence, Predictors, and Outcomes.

BACKGROUND: Scarce data exist on the evolution of device-related thrombus (DRT) after left atrial appendage closure (LAAC). OBJECTIVES: This study sought to assess the incidence, predictors, and clinical impact of persistent and recurrent DRT in LAAC recipients. METHODS: Data were obtained from an international multicenter registry including 237 patients diagnosed with DRT after LAAC. Of these, 214 patients with a subsequent imaging examination after the initial diagnosis of DRT were included. Unfavorable evolution of DRT was defined as either persisting or recurrent DRT. RESULTS: DRT resolved in 153 (71.5%) cases and persisted in 61 (28.5%) cases. Larger DRT size (OR per 1-mm increase: 1.08; 95% CI: 1.02-1.15; P = 0.009) and female (OR: 2.44; 95% CI: 1.12-5.26; P = 0.02) were independently associated with persistent DRT. After DRT resolution, 82 (53.6%) of 153 patients had repeated device imaging, with 14 (17.1%) cases diagnosed with recurrent DRT. Overall, 75 (35.0%) patients had unfavorable evolution of DRT, and the sole predictor was average thrombus size at initial diagnosis (OR per 1-mm increase: 1.09; 95% CI: 1.03-1.16; P = 0.003), with an optimal cutoff size of 7 mm (OR: 2.51; 95% CI: 1.39-4.52; P = 0.002). Unfavorable evolution of DRT was associated with a higher rate of thromboembolic events compared with resolved DRT (26.7% vs 15.1%; HR: 2.13; 95% CI: 1.15-3.94; P = 0.02). CONCLUSIONS: About one-third of DRT events had an unfavorable evolution (either persisting or recurring), with a larger initial thrombus size (particularly >7 mm) portending an increased risk. Unfavorable evolution of DRT was associated with a 2-fold higher risk of thromboembolic events compared with resolved DRT.

Predictors of Device-Related Thrombus Following Percutaneous Left Atrial Appendage Occlusion.

BACKGROUND: Device-related thrombus (DRT) has been considered an Achilles' heel of left atrial appendage occlusion (LAAO). However, data on DRT prediction remain limited. OBJECTIVES: This study constructed a DRT registry via a multicenter collaboration aimed to assess outcomes and predictors of DRT. METHODS: Thirty-seven international centers contributed LAAO cases with and without DRT (device-matched and temporally related to the DRT cases). This study described the management patterns and mid-term outcomes of DRT and assessed patient and procedural predictors of DRT. RESULTS: A total of 711 patients (237 with and 474 without DRT) were included. Follow-up duration was similar in the DRT and no-DRT groups, median 1.8 years (interquartile range: 0.9-3.0 years) versus 1.6 years (interquartile range: 1.0-2.9 years), respectively (P = 0.76). DRTs were detected between days 0 to 45, 45 to 180, 180 to 365, and >365 in 24.9%, 38.8%, 16.0%, and 20.3% of patients. DRT presence was associated with a higher risk of the composite endpoint of death, ischemic stroke, or systemic embolization (HR: 2.37; 95% CI, 1.58-3.56; P < 0.001) driven by ischemic stroke (HR: 3.49; 95% CI: 1.35-9.00; P = 0.01). At last known follow-up, 25.3% of patients had DRT. Discharge medications after LAAO did not have an impact on DRT. Multivariable analysis identified 5 DRT risk factors: hypercoagulability disorder (odds ratio [OR]: 17.50; 95% CI: 3.39-90.45), pericardial effusion (OR: 13.45; 95% CI: 1.46-123.52), renal insufficiency (OR: 4.02; 95% CI: 1.22-13.25), implantation depth >10 mm from the pulmonary vein limbus (OR: 2.41; 95% CI: 1.57-3.69), and non-paroxysmal atrial fibrillation (OR: 1.90; 95% CI: 1.22-2.97). Following conversion to risk factor points, patients with ≥2 risk points for DRT had a 2.1-fold increased risk of DRT compared with those without any risk factors. CONCLUSIONS: DRT after LAAO is associated with ischemic events. Patient- and procedure-specific factors are associated with the risk of DRT and may aid in risk stratification of patients referred for LAAO.

Intracardiac echocardiography for guidance of transcatheter left atrial appendage occlusion: An expert consensus document.

Transcatheter left atrial appendage occlusion (LAAO) is an increasingly used alternative to oral anticoagulation in selected patients with atrial fibrillation. Intraprocedural imaging is a crucial for a successful intervention, with transesophageal echocardiography (TEE) as the current gold standard. Since some important limitations may affect TEE use, intracardiac echocardiography (ICE) is increasingly used as an alternative to TEE for guiding LAAO. The lack of a standardized imaging protocol has slowed the adoption of ICE into clinical practice. On the basis of current research and expert consensus, this paper provides a protocol for ICE support of left atrial appendage occlusion.

Italian Multicenter Registry of Bare Metal Stent Use in Modern Percutaneous Coronary Intervention Era (AMARCORD): A multicenter observational study.

OBJECTIVES: We aimed to evaluate the use of bare metal stent (BMS) implantation in current percutaneous coronary intervention (PCI) era, focusing on indications for use and clinical outcomes. BACKGROUND: Limited data on BMS usage in current clinical practice are available. METHODS: All patients who underwent PCI with at least one BMS implantation in 18 Italian centers from January 1, 2013 to December 31, 2017, were included in our registry. Rates of BMS use and reasons for BMS implantations were reported for the overall study period and for each year. Primary outcomes were mortality, bleeding (Bleeding Academic Research Consortium-BARC and Thrombolysis in Myocardial Infarction-TIMI non-CABG definitions), and major adverse cardiac events (MACE) defined as the composite of all-cause and cardiac death, any myocardial infarction, target vessel revascularization, or any stent thrombosis. RESULTS: Among 58,879 patients undergoing PCI in the study period, 2,117 (3.6%) patients (mean age 73 years, 69.7% males, 73.3% acute coronary syndrome) were treated with BMS implantation (2,353 treated lesions). The rate of BMS implantation progressively decreased from 10.1% (2013) to 0.3% (2017). Main reasons for BMS implantation were: ST-elevation myocardial infarction (STEMI) (23.1%), advanced age (24.4%), and physician's perception of high-bleeding risk (34.0%). At a mean follow-up of 2.2 ± 1.5 years, all-cause and cardiac mortality were 25.6 and 12.7%, respectively; MACE rate was 35.3%, any bleeding rate was 13.0% (BARC 3-5 bleeding 6.3%, TIMI non-CABG major bleeding 6.1%). CONCLUSION: In a large, contemporary, real-world, multicenter registry, BMS use progressively reduced over the last 5 years. Main reasons for BMS implantation were STEMI, advanced age, and physician's perception of high-bleeding risk. High rates of mortality and MACE were observed in this real-world high-risk population.

N-terminal fragment of B-type natriuretic peptide predicts coexisting subclinical heart and vessel disease.

BACKGROUND: Identification of preclinical cardiovascular disease represents a challenge. We evaluate N-terminal proB-type natriuretic peptides (NT-proBNP) as markers of both cardiac and vascular subclinical disease in a community-based study including asymptomatic middle- aged study participants. METHODS AND RESULTS: In total, 807 study participants without previous cardiovascular disease were recruited. They underwent thorough laboratory assessment (including NT-proBNP), ultrasound examination of heart and evaluation of coronary calcium score and carotid intima-media thickness, by computed tomography and ultrasound, respectively.Cardiac and vascular disease were defined as one among left ventricular (LV) ejection fraction less than 50% (3.1%), E/E' ratio more than 15 (9%), LV mass index more than 115 in men or more than 95 g/m in women (20%), LV end diastolic diameter more than 55 mm (2.5%), coronary calcium score more than 100 AU (13%), or carotid intima-media thickness more than 1.2 mm (21%), respectively. NT-proBNP [OR, 1.275; 95% (confidence interval) CI, 1.007-1.613, P < 0.001], 10-year Framingham risk score (FRS; OR 1.132; 95% CI, 1.058-1.212, P < 0.001) and lower creatinine clearance (OR, 0.983; 95% CI, 0.971-0.994, P < 0.001) predicted cardiac (220, 27%), whereas 10-year Framingham risk score (OR, 1.340; 95% CI, 1.245-1.674, P < 0.001) and NT-proBNP (OR, 1.501; 95% CI, 1.181-1.907, P < 0.001) predicted vascular involvement (215, 26%), at multivariate analysis. In total, 84 study participants (10.1%) had coexisting cardiac and vascular disease. NT-proBNP increased linearly from health study participants to study participants with only cardiac or vascular involvement, up to coexisting cardiovascular disease. CONCLUSION: Coexisting cardiac and vascular involvement in asymptomatic study participants is common. Along with traditional risk factors, NT-proBNP appears a valuable biomarker for global subclinical heart and vessels disease.

The search for efficient diagnostic and prognostic biomarkers of heart failure.

Several biomarkers have been tested for screening, diagnosis and prognosis purposes, as well as to guide treatment in heart failure, but only the assay of circulating B-type natriuretic peptides has widely recognized applications for clinical decision-making. Natriuretic peptides are sensitive in detecting the clinically overt or subclinical myocardial damage, but their plasma levels are increased following every generic insult to the cardiovascular system. Novel biomarkers are required to identify specific pathways of disease progression, such as diverse neurohormonal axes activation, inflammation and fibrogenesis, and to act as a tool for therapeutic tailoring. In this view, Gal-3 and ST-2 assays seem very promising, given their involvement in mechanisms of cardiac fibrosis and their prognostic value.

N-terminal prob-type natriuretic peptide is a marker of vascular remodelling and subclinical atherosclerosis in asymptomatic hypertensives.

BACKGROUND: Arterial hypertension is a main determinant of arterial remodelling and atherosclerosis. Coronary artery calcium score and carotid intima-media thickness are recognized indices of vascular remodelling. Established biohumoral markers for the diagnosis of atherosclerosis are still lacking in asymptomatic subjects with hypertension. OBJECTIVES: We aimed to test the association of plasma N-terminal pro B-type natriuretic peptide concentrations with either coronary artery calcium score or carotid intima-media thickness in asymptomatic hypertensive subjects. METHODS: We conducted a case-control study on 436 hypertensi.ve and 436 age/sex-matched normotensive subjects from the population of the Montignoso HEart and Lung Project, a community-based study of asymptomatic general population ≥45 years. Subjects underwent N-terminal pro B-type natriuretic peptide measurement, echocardiography and evaluation of coronary artery calcium score and carotid intima-media thickness. RESULTS: Hypertensive subjects had higher median coronary artery calcium score (60 (interquartile range, 30-112) vs. 15 (interquartile range 3-70) Agatson units, p = 0.007), carotid intima-media thickness (8.6 (interquartile range 7.5-9.1) vs. 7.9 (7.1-8.4) µm, p < 0.001) and indexed left ventricular mass (101 (interquartile range 82-126) vs. 87 (63-91) mg/m2, p = 0.03) than controls, with no differences in left ventricular ejection fraction, diameters, E/E', left atrial area. N-terminal pro B-type natriuretic peptide concentrations were higher in hypertensive subjects with either coronary artery calcium score (p = 0.008) or carotid intima-media thickness >75th (p < 0.006) percentile and highest in combined coronary artery calcium score/carotid intima-media thickness >75th percentile (p = 0.021). In multivariable analysis, N-terminal pro B-type natriuretic peptide independently predicted either coronary artery calcium score or carotid intima-media thickness >75th percentile, but only in hypertensive subjects (odds ratio = 1.87, 95% confidence interval 1.30-2.74, p = 0.001 and odds ratio = 1.99, 95% confidence interval 1.43-2.76, p = 0.001). CONCLUSIONS: In asymptomatic subjects with hypertension, N-terminal pro B-type natriuretic peptide is a marker of hypertension-mediated preclinical vascular disease.

Metabolic exercise test data combined with cardiac and kidney indexes, the MECKI score: a multiparametric approach to heart failure prognosis.

OBJECTIVES: We built and validated a new heart failure (HF) prognostic model which integrates cardiopulmonary exercise test (CPET) parameters with easy-to-obtain clinical, laboratory, and echocardiographic variables. BACKGROUND: HF prognostication is a challenging medical judgment, constrained by a magnitude of uncertainty. METHODS: Our risk model was derived from a cohort of 2716 systolic HF patients followed in 13 Italian centers. Median follow up was 1041days (range 4-5185). Cox proportional hazard regression analysis with stepwise selection of variables was used, followed by cross-validation procedure. The study end-point was a composite of cardiovascular death and urgent heart transplant. RESULTS: Six variables (hemoglobin, Na(+), kidney function by means of MDRD, left ventricle ejection fraction [echocardiography], peak oxygen consumption [% pred] and VE/VCO2 slope) out of the several evaluated resulted independently related to prognosis. A score was built from Metabolic Exercise Cardiac Kidney Indexes, the MECKI score, which identified the risk of study end-point with AUC values of 0.804 (0.754-0.852) at 1year, 0.789 (0.750-0.828) at 2years, 0.762 (0.726-0.799) at 3years and 0.760 (0.724-0.796) at 4years. CONCLUSIONS: This is the first large-scale multicenter study where a prognostic score, the MECKI score, has been built for systolic HF patients considering CPET data combined with clinical, laboratory and echocardiographic measurements. In the present population, the MECKI score has been successfully validated, performing very high AUC.