Long-term outcomes of left atrial appendage occlusion in high-risk atrial fibrillation patients: 4-year follow up data.

Long-term follow-up data of left atrial appendage (LAA) occlusion in patients with atrial fibrillation (AF) are sparse. To address these data gaps, we analysed the 4-year outcomes of AF patients following LAA occlusion. The was a retrospective cohort study of high-risk patients with AF who underwent successful implantation of the Amulet device at our center between 2014 and 2017. Study endpoints were the rate of stroke, major bleeding and all-cause mortality. We included 71 patients (35.2% females) with a median age of 78 (IQR 73-82) years. Over a median follow-up period of 46 (IQR 19-56) months, the annual rate of ischemic stroke was 1.06 events/100 patient-years (95% CI 0-2.35), hemorrhagic stroke was 1.06 events/100 patient-years (95% CI 0-2.35) and major extracranial bleeding that required unplanned hospital admission was 1.84 events/100 patient-years (95% CI 0.25-3.43). A total of 28 (39.4%) patients died during this period with an annual mortality rate of 10.29 events/100 patient-years (95% CI 7.25-13.32). Our experience suggests that LAA occlusion using the Amulet device appears to be associated with a low risk of ischemic stroke in high-risk AF patients who are deemed unsuitable for oral anticoagulation; however, these patients have a high rate of mortality over the medium to long-term follow-up, and an ongoing significant risk of bleeding and thrombotic events.

Percutaneous left atrial appendage occlusion following successful treatment of large bi-atrial thrombi in a patient with atrial fibrillation: a case report.

Background: Atrial fibrillation (AF) is a well-established risk factor for intracardiac thrombosis. Left atrial appendage occlusion (LAAO) is emerging as a viable alternative to oral anticoagulation (OAC) for high-risk AF patients who are contraindicated to long-term OAC. Case summary: A 74-year-old man with a history of permanent AF and subdural haemorrhage on warfarin therapy was referred to our facility for further management. Cardiac CT imaging revealed large bi-atrial thrombi for which apixaban therapy was initiated. Serial imaging over nine months showed gradual shrinkage and then resolution of the thrombi. In line with the patient's preference to avoid life-long OAC, he received LAAO using an Amplatzer™ Amulet™ device. Follow-up transoesophageal echocardiography showed a well-seated device with no leak and no thrombus. Discussion: We discussed the key issues surrounding management of bi-atrial thrombi and the decision to perform LAAO in these circumstances, relying on shared decision making and multi-disciplinary team input.

The measurement of nitric oxide and its metabolites in biological samples by ozone-based chemiluminescence.

A plethora of publications on techniques and methodologies for measuring nitric oxide (NO) or reaction products of NO (NO metabolites) has served in recent years to complicate and confuse the majority of researchers interested in this field. Here, we provide a practical approach and summarize the key issues and corresponding solutions regarding quantification with the use of ozone-based chemiluminescence, which is the most accurate, sensitive, and widely used NO detection method. We have drawn on the vast experience of leaders in the field to produce this consensus, but the views and implications presented herein represent our own, and we limit our advice to those techniques with which we have direct experience. Hopefully, this guide will allow authors to make more informed decisions regarding NO metabolite measurement methodology, without the need for each subsequent group to rediscover previously observed advantages and pitfalls.

NO metabolite flux across the human coronary circulation.

OBJECTIVES: The theory of a red blood cell derived nitric oxide (NO) reserve conserving NO bioactivity and delivering NO as a function of oxygen demand has been the subject of much interest. We identified the human coronary circulation as an ideal model system in which to analyse NO metabolites because of its large physiological oxygen gradient. Our objective was to identify whether oxygen drove apportion between various NO metabolite species across a single vascular bed. METHODS: Plasma and red blood cell NO metabolites were assessed from the left main coronary artery, coronary sinus and pulmonary artery (providing cross heart and cross pulmonary analysis) of healthy subjects under resting conditions and following administration of an inhibitor of NO biosynthesis. Physiological parameters and angiographic data were monitored throughout the study. RESULTS: Under baseline conditions we observed significant metabolite flux upon the transit of blood across the coronary and pulmonary vascular beds. Whilst there was no net loss of NO through the coronary circulation (p=0.0759), plasma nitrite/protein NO (excluding nitrate) (p=0.0279) and red blood cell sulphanilamide labile signal (p=0.0143) decreased whereas haemoglobin-bound NO increased three-fold (p=0.005). These changes across the coronary circulation were reversed through the pulmonary circuit with red blood cell sulphanilamide labile signal (p=0.0143) and plasma nitrite/protein NO (p=0.0279) increasing and haemoglobin-bound NO decreasing. Blockade of NO synthesis increased mean arterial blood pressure (p<0.01) and reduced coronary artery diameter (p<0.05), however we observed similar apportion of NO metabolites across the heart and lung with no net loss or gain in total NO metabolites. CONCLUSIONS: For the first time in human subjects across the resting coronary circulation we reveal significant re-apportionment of NO between metabolite species which correlate with haemoglobin oxygen saturation. These changes occur even within the transit time of blood across this single vascular bed. We demonstrate no net loss/gain of NO from the total metabolite pool across the coronary circulation even where NO biosynthesis is inhibited.

Outcome of left atrial appendage occlusion in high-risk patients.

OBJECTIVE: Percutaneous left atrial appendage (LAA) occlusion can be an interventional alternative to oral anticoagulation for stroke prevention in patients with atrial fibrillation. METHODS: We delivered LAA occlusion therapy using a standardised approach to patient referral, multidisciplinary team assessment, implant criteria, imaging and follow-up. We analysed patient characteristics, efficacy and safety of the implant procedure, and 12-month outcomes. RESULTS: Of 143 referrals from October 2014 to December 2016, 83 patients (age 76±8years, 32.5% female, mean CHAD2S2-VASc score 4 ±1) were offered LAA occlusion. Eighty (95.3%) had previous major bleeding (intracranial in 59%). LAA occluder implantation with an Amulet device was successful in 82 (98.8%), with periprocedural major adverse events occurring in 5 (6.0%) patients (2 device embolisations including 1 death, 2 major bleeds). Cardiac imaging in 75 (94%) patients 2months following implant showed device-related thrombus in 1 case (1.3%) and minor (<5mm) device leaks in 13 (17.1%). Over a median 12-month follow-up, 3 (3.8%) ischaemic strokes, 2 (2.5%) haemorrhagic strokes and 5 (6.3%) major extracranial bleeds occurred. All-cause mortality was 10%, with most deaths (7, 87.5%) due to non-cardiovascular causes. CONCLUSIONS: LAA occlusion may be a reasonable option for stroke prevention inhigh-risk patients with atrial fibrillation ineligible for anticoagulation. However, procedural complication rates are not insignificant, and patients remain at risk of serious adverse events and death even after successful implant.

Detection of human red blood cell-bound nitric oxide.

Major disparities in reported levels of basal human nitric oxide metabolites have resulted in a recent literature focusing almost exclusively on methods. We chose to analyze triiodide chemiluminescence, drawn by the prospect of identifying why the most commonly employed assay in nitric oxide biology typically yielded lower metabolite values, compared with several other techniques. We found that the sensitivity of triiodide was greatly affected by the auto-capture of nitric oxide by deoxygenated cell-free heme in the reaction chamber. Potential contaminants and signal losses were also associated with standard sample purification procedures and the chemistry involved in nitrite removal. To inhibit heme nitric oxide auto-capture, we added potassium ferricyanide to the triiodide reagent, reasoning this would provide a more complete detection of any liberated nitric oxide. From human venous blood samples, we established nitric oxide levels ranging from 0.000178 to 0.00024 mol nitric oxide/mol hemoglobin. We went on to find significantly elevated nitric oxide levels in venous blood taken from diabetic patients in comparison to healthy controls (p < 0.0001). We concluded that the lack of signals reported of late by several groups using triiodide chemiluminescence for the detection of hemoglobin-bound nitric oxide may not represent levels on the border of assay sensitivity but rather underestimated values because of methodological limitations. We therefore stress the need for assay systems to be developed that differentiate between individual nitric oxide metabolite species and overcome the limitations we outline, allowing accurate conclusions to be drawn regarding physiological nitric oxide metabolite levels.