Determinants of label non-adherence to non-vitamin K oral anticoagulants in patients with newly diagnosed atrial fibrillation.

Aims: To evaluate the extent and determinants of off-label non-vitamin K oral anticoagulant (NOAC) dosing in newly diagnosed Dutch AF patients. Methods and results: In the DUTCH-AF registry, patients with newly diagnosed AF (<6 months) are prospectively enrolled. Label adherence to NOAC dosing was assessed using the European Medicines Agency labelling. Factors associated with off-label dosing were explored by multivariable logistic regression analyses. From July 2018 to November 2020, 4500 patients were registered. The mean age was 69.6 ± 10.5 years, and 41.5% were female. Of the 3252 patients in which NOAC label adherence could be assessed, underdosing and overdosing were observed in 4.2% and 2.4%, respectively. In 2916 (89.7%) patients with a full-dose NOAC recommendation, 4.6% were underdosed, with a similar distribution between NOACs. Independent determinants (with 95% confidence interval) were higher age [odds ratio (OR): 1.01 per year, 1.01-1.02], lower renal function (OR: 0.96 per ml/min/1.73 m2, 0.92-0.98), lower weight (OR: 0.98 per kg, 0.97-1.00), active malignancy (OR: 2.46, 1.19-5.09), anaemia (OR: 1.73, 1.08-2.76), and concomitant use of antiplatelets (OR: 4.93, 2.57-9.46). In the 336 (10.3%) patients with a reduced dose NOAC recommendation, 22.9% were overdosed, most often with rivaroxaban. Independent determinants were lower age (OR: 0.92 per year, 0.88-0.96) and lower renal function (OR: 0.98 per ml/min/1.73 m2, 0.96-1.00). Conclusion: In newly diagnosed Dutch AF patients, off-label dosing of NOACs was seen in only 6.6% of patients, most often underdosing. In this study, determinants of off-label dosing were age, renal function, weight, anaemia, active malignancy, and concomitant use of antiplatelets.

A single-centre prospective evaluation of left bundle branch area pacemaker implantation characteristics.

BACKGROUND: Left bundle branch area pacing (LBBAP) has recently been introduced as a physiological pacing technique with synchronous left ventricular activation. It was our aim to evaluate the feasibility and learning curve of the technique, as well as the electrical characteristics of LBBAP. METHODS AND RESULTS: LBBAP was attempted in 80 consecutive patients and electrocardiographic characteristics were evaluated during intrinsic rhythm, right ventricular septum pacing (RVSP) and LBBAP. Permanent lead implantation was successful in 77 of 80 patients (96%). LBBAP lead implantation time and fluoroscopy time shortened significantly from 33 ± 16 and 21 ± 13 min to 17 ± 5 and 12 ± 7 min, respectively, from the first 20 to the last 20 patients. Left bundle branch (LBB) capture was achieved in 54 of 80 patients (68%). In 36 of 45 patients (80%) with intact atrioventricular conduction and narrow QRS, an LBB potential (LBBpot) was present with an LBBpot to onset of QRS interval of 22 ± 6 ms. QRS duration increased significantly more during RVSP (141 ± 20 ms) than during LBBAP (125 ± 19 ms), compared to 130 ± 30 ms without pacing. An even clearer difference was observed for QRS area, which increased significantly more during RVSP (from 32 ± 16 µVs to 73 ± 20 µVs) than during LBBAP (41 ± 15 µVs). QRS area was significantly smaller in patients with LBB capture compared to patients without LBB capture (43 ± 18 µVs vs 54 ± 21 µVs, respectively). In patients with LBB capture (n = 54), the interval from the pacing stimulus to R­wave peak time in lead V6 was significantly shorter than in patients without LBB capture (75 ± 14 vs 88 ± 9 ms, respectively). CONCLUSION: LBBAP is a safe and feasible technique, with a clear learning curve that seems to flatten after 40-60 implantations. LBB capture is achieved in two-thirds of patients. Compared to RVSP, LBBAP largely maintains ventricular electrical synchrony at a level close to intrinsic (narrow QRS) rhythm.

Contemporary management of patients with atrial fibrillation in the Netherlands and Belgium: a report from the EORP-AF long-term general registry.

BACKGROUND: Contemporary data regarding the characteristics, treatment and outcomes of patients with atrial fibrillation (AF) are needed. We aimed to assess these data and guideline adherence in the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) long-term general registry. METHODS: We analysed 967 patients from the EORP-AF long-term general registry included in the Netherlands and Belgium from 2013 to 2016. Baseline and 1­year follow-up data were gathered. RESULTS: At baseline, 887 patients (92%) received anticoagulant treatment. In 88 (10%) of these patients, no indication for chronic anticoagulant treatment was present. A rhythm intervention was performed or planned in 52 of these patients, meaning that the remaining 36 (41%) were anticoagulated without indication. Forty patients were not anticoagulated, even though they had an indication for chronic anticoagulation. Additionally, 63 of the 371 patients (17%) treated with a non-vitamin K antagonist oral anticoagulant (NOAC) were incorrectly dosed. In total, 50 patients (5%) were overtreated and 89 patients (9%) were undertreated. However, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was still low with 4.2% (37 patients). CONCLUSIONS: Overtreatment and undertreatment with anticoagulants are still observable in 14% of this contemporary, West-European AF population. Still, MACCE occurred in only 4% of the patients after 1 year of follow-up.

Clinical determinants of early spontaneous conversion to sinus rhythm in patients with atrial fibrillation.

BACKGROUND: The current standard of care for acute atrial fibrillation (AF) focuses primarily on immediate restoration of sinus rhythm by cardioversion, although AF often terminates spontaneously. OBJECTIVE: To identify determinants of early spontaneous conversion (SCV) in patients presenting at the emergency department (ED) because of AF. METHODS: An observational study was performed of patients who visited the ED with documented AF between July 2014 and December 2016. The clinical characteristics and demographics of patients with and without SCV were compared. RESULTS: We enrolled 943 patients (age 69 ± 12 years, 47% female). SCV occurred within 3 h of presentation in 158 patients (16.8%). Logistic regression analysis showed that duration of AF <24 h [odds ratio (OR) 7.7, 95% confidence interval (CI) 3.5-17.2, p < 0.001], left atrial volume index <42 ml/m2 (OR 1.8, 95% CI 1.2-2.8, p = 0.010), symptoms of near-collapse at presentation (OR 2.4, 95% CI 1.2-5.1, p = 0.018), a lower body mass index (BMI) (OR 0.9, 95% CI 0.91-0.99, p = 0.028), a longer QTc time during AF (OR 1.01, 95% CI 1.0-1.02, p = 0.002) and first-detected AF (OR 2.5, 95% CI 1.6-3.9, p < 0.001) were independent determinants of early SCV. CONCLUSION: Early spontaneous conversion of acute AF occurs in almost one-sixth of admitted patients during a short initial observation in the ED. Spontaneous conversion is most likely to occur in patients with first-onset, short-duration AF episodes, lower BMI, and normal left atrial size.

Idiopathic atrial fibrillation patients rapidly outgrow their low thromboembolic risk: a 10-year follow-up study.

BACKGROUND: Healthy atrial fibrillation (AF) patients will eventually outgrow their low thromboembolic risk. The purpose of this study is to compare the development of cardiovascular disease in healthy AF patients as compared to healthy sinus rhythm patients and to assess appropriate anticoagulation treatment. METHODS: Forty-one idiopathic paroxysmal AF patients (56 ± 10 years, 66% male) were compared with 45 healthy sinus rhythm patients. Patients were free of hypertension, antihypertensive and antiarrhythmic drugs, diabetes, congestive heart failure, coronary artery or peripheral vascular disease, previous stroke, thyroid, pulmonary and renal disease, and structural abnormalities on echocardiography. RESULTS: Baseline characteristics and echocardiographic parameters were the same in both groups. During 10.7 ± 1.6 years, cardiovascular disease and all-cause death developed significantly more often in AF patients as compared to controls (63% vs 31%, log rank p < 0.001). Even after the initial 5 years of follow-up, survival curves show divergent patterns (log rank p = 0.006). Mean duration to reach a CHA2DS2-VASc score > 1 among AF patients was 5.1 ± 3.0 years. Five of 24 (21%) patients with CHA2DS2-VASc > 1 did not receive oral anticoagulation therapy at follow-up. Mean duration of over- or undertreatment with oral anticoagulation in patients with CHA2DS2-VASc > 1 was 5 ± 3.0 years. CONCLUSION: The majority of recently diagnosed healthy AF patients develop cardiovascular diseases with a consequent change in thromboembolic risk profile within a short time frame. A comprehensive follow-up of this patient category is necessary to avoid over- and undertreatment with anticoagulants.

Visualisation of coronary venous anatomy by computed tomography angiography prior to cardiac resynchronisation therapy implantation.

BACKGROUND: The purpose of this study was to illustrate the additive value of computed tomography angiography (CTA) for visualisation of the coronary venous anatomy prior to cardiac resynchronisation therapy (CRT) implantation. METHODS: Eighteen patients planned for CRT implantation were prospectively included. A specific CTA protocol designed for visualisation of the coronary veins was carried out on a third-generation dual-source CT platform. Coronary veins were semi-automatically segmented to construct a 3D model. CTA-derived coronary venous anatomy was compared with intra-procedural fluoroscopic angiography (FA) in right and left anterior oblique views. RESULTS: Coronary venous CTA was successfully performed in all 18 patients. CRT implantation and FA were performed in 15 patients. A total of 62 veins were visualised; the number of veins per patient was 3.8 (range: 2-5). Eighty-five per cent (53/62) of the veins were visualised on both CTA and FA, while 10% (6/62) were visualised on CTA only, and 5% (3/62) on FA only. Twenty-two veins were present on the lateral or inferolateral wall; of these, 95% (21/22) were visualised by CTA. A left-sided implantation was performed in 13 patients, while a right-sided implantation was performed in the remaining 2 patients because of a persistent left-sided superior vena cava with no left innominate vein on CTA. CONCLUSION: Imaging of the coronary veins by CTA using a designated protocol is technically feasible and facilitates the CRT implantation approach, potentially improving the outcome.

Stroke risk in patients with device-detected atrial high-rate episodes.

Cardiovascular implantable electronic devices (CIEDs) can detect atrial arrhythmias, i. e. atrial high-rate episodes (AHRE). The thrombo-embolic risk in patients showing AHRE appears to be lower than in patients with clinical atrial fibrillation (AF) and it is unclear whether the former will benefit from oral anticoagulants. Based on currently available evidence, it seems reasonable to consider antithrombotic therapy in patients without documented AF showing AHRE >24 hours and a CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes mellitus, prior stroke [doubled], vascular disease, age 65-74 years and female sex) ≥1, awaiting definite answers from ongoing randomised clinical trials. In patients with AHRE <24 hours, current literature does not support starting oral anticoagulation. In these patients, intensifying CIED read-outs can be considered to find progression in AHRE duration sooner, enhancing timely stroke prevention. The notion that AHRE and stroke coincide perseveres but should be abandoned since CIED data show a clear disconnect.

Identifying delayed left ventricular lateral wall activation in patients with non-specific intraventricular conduction delay using coronary venous electroanatomical mapping.

BACKGROUND: Delayed left ventricular (LV) lateral wall activation is considered the electrical substrate that characterises patients suitable for cardiac resynchronisation therapy (CRT). Although typically associated with left bundle branch block, delayed LV lateral wall activation may also be present in patients with non-specific intraventricular conduction delay (IVCD). We assessed LV lateral wall activation in a cohort of CRT candidates with IVCD using coronary venous electroanatomical mapping, and investigated whether baseline QRS characteristics on the ECG can identify delayed LV lateral wall activation in this group of patients. METHODS: Twenty-three consecutive CRT candidates with IVCD underwent intra-procedural coronary venous electroanatomical mapping using EnSite NavX. Electrical activation time was measured in milliseconds from QRS onset and expressed as percentage of QRS duration. LV lateral wall activation was considered delayed if maximal activation time measured at the LV lateral wall (LVLW-AT) exceeded 75 % of the QRS duration. QRS morphology, duration, fragmentation, axis deviation, and left anterior/posterior fascicular block were assessed on baseline ECGs. RESULTS: Delayed LV lateral wall activation occurred in 12/23 patients (maximal LVLW-AT = 133 ± 20 ms [83 ± 5 % of QRS duration]). In these patients, the latest activated region was consistently located on the basal lateral wall. QRS duration, and prevalence of QRS fragmentation and left/right axis deviation, and left anterior/posterior fascicular block did not differ between patients with and without delayed LV lateral wall activation. CONCLUSION: Coronary venous electroanatomical mapping can be used at the time of CRT implantation to determine the presence of delayed LV lateral wall activation in patients with IVCD. QRS characteristics on the ECG seem unable to identify delayed LV lateral wall activation in this subgroup of patients.

Conduction recovery in patients with recurrent atrial fibrillation after pulmonary vein isolation using multi-electrode duty cycled radiofrequency ablation.

INTRODUCTION: The pulmonary vein ablation catheter (PVAC) is designed for pulmonary vein isolation (PVI). Electrical reconnection of pulmonary veins is believed to result in AF recurrence. The purpose of this study was to establish the location and extent of PV reconnection after PVI with the PVAC catheter. METHODS AND RESULTS: Eighty-two patients (79 % male, age 60 ± 9 years) that underwent a redo procedure for recurrent AF after PVAC ablation were assessed for prevalence and location of reconnection. The number of reconnected PV's was 0, 1, 2, 3, or 4 in 2 (2.4 %), 14 (17 %), 23 (28 %), 28 (34 %), and 15 (18 %) patients, respectively. Reconnection of left superior, left inferior, left common, right superior, and right inferior PV's was found in 66, 63, 83, 57, and 67 %, respectively (p = 0.48). In the left PV's, reconnection was located significantly more anterior than posterior; LSPV anterior 32/70 vs posterior 13/70 (p < 0.01), LIPV anterior 26/70 vs posterior 9/70 (p < 0.01). In the right PV's reconnection was distributed equally in all quadrants. Different modes of RF delivery during PVAC ablation (bipolar/unipolar 2:1 [n = 35] vs. 4:1 [n = 47]) yielded comparable rates of PV reconnection. During follow-up (median 296 days) no AF/AT was documented in 57 patients (70 %). CONCLUSION: Almost all patients (98 %) with AF after PVAC ablation show reconnection of at least one PV. All PV's are equally likely to show reconnection. In the left PV's, reconnection was found more often anteriorly than posteriorly. During pulmonary vein isolation with the PVAC catheter, prevalent sites of reconnection deserve close attention to increase success.

Heterophilic antibodies may be a cause of falsely low total IGF1 levels.

BACKGROUND: A low serum total IGF1 is considered as a diagnostic indicator of GH deficiency (GHD) in the presence of hypopituitarism. Introduction of IRMA and chemiluminescent immunometric assay (CLIA) IGF1 immunoassays has introduced endogenous antibodies as a new source of interference. In general, this goes unnoticed and might lead to unnecessary diagnostic and therapeutic interventions. CASE: A 56-year-old man was referred with a decline in physical performance, unexplained osteopenia, and weight loss of 3 kg over the past 8 months. Although clinical signs and symptoms were unremarkable, laboratory results pointed to secondary hypothyroidism and secondary hypogonadism. In addition, the serum total IGF1 level (CLIA; Siemens Medical Solutions Diagnostics) was in the low normal range. Two GH stimulation tests were performed, but these tests did not support the diagnosis GHD. Moreover, IGF1 bioactivity measured by the kinase receptor activation assay was normal. Interference of heterophilic antibodies was considered. After pretreatment with specific heterophilic blocking tubes that contain blocking reagents to eliminate heterophilic antibodies, serum-free thyroxine, testosterone, and IGF1 levels turned out to be normal. CONCLUSION: To the best of our knowledge, we here describe the first case in the literature of a patient with low serum total IGF1 levels due to interference from heterophilic antibodies in the used IGF1 immunoassay. When confronted with low-IGF1 levels that do not fit the clinical picture, interference of heterophilic antibodies should be considered in the differential diagnosis.

Screening for pulmonary arteriovenous malformations using transthoracic contrast echocardiography: a prospective study.

Pulmonary arteriovenous malformations (PAVMs) are associated with severe neurological complications in patients with hereditary haemorrhagic telangiectasia (HHT). The objective of the present study was to prospectively establish the diagnostic value of transthoracic contrast echocardiography (TTCE) as a screening technique for PAVM using chest high-resolution computed tomography (HRCT) as the gold standard for PAVMs. All consecutive adult patients referred for HHT screening underwent a chest HRCT (n = 299), TTCE (n = 281), arterial blood gas analysis (n = 291), shunt fraction measurement (n = 111) and chest radiography (n = 296). TTCE was positive in 87 (58.8%), 12 (16.7%) and four (6.7%) patients, and chest HRCT was positive in 54 (36.5%), three (4.2%) and zero (0%) patients with a definite, possible and negative clinical diagnosis of HHT, respectively. Two patients with a negative TTCE were diagnosed with PAVMs after computed tomography; in both cases the PAVMs were too small to be treated by embolotherapy. The sensitivity of TTCE was 97% (95% confidence interval (CI) 93.6-98.3) and negative predictive value 99% (95% CI 96.9-99.8). The other diagnostic tests showed a considerable lower diagnostic value. The present prospective study shows that transthoracic contrast echocardiography has an excellent diagnostic value and can be used as an initial screening procedure for pulmonary arteriovenous malformations. The high false-positive rate of transthoracic contrast echocardiography possibly represents microscopic pulmonary arteriovenous malformations.

New-onset and persistent migraine early after percutaneous atrial septal defect closure disappear at follow-up.

AIMS: Recently we reported that percutaneous atrial septal defect (ASD) closure had no influence on the prevalence of migraine during a short followup period. 12 % of patients however developed a new-onset migraine after the ASD closure. As it has been suggested that the closing device might induce or maintain migraine temporarily, we were interested in the prevalence of migraine at longer follow-up. METHODS: All 75 patients included in the previous study, received the same structured headache questionnaire. A neurologist, blinded to previous data, diagnosed migraine with or without aura (MA+ or MA-) according to the International Headache Criteria. McNemar paired X2 test was used to evaluate changes in the occurrence of migraine. RESULTS: Seventy-one patients (94.7%) answer the questionnaire (55 women, mean age at closure 51 +/- 18 years). Mean follow-up time was 52 +/- 13 months. The overall migraine prevalence decreased from 30.7% before to 22.5% after closure (P=0.21). A significant reduction was noted in patients with new-onset migraine early after closure (n=7), where migraine disappeared in 6 patients (P=0.031). In the group with persistent migraine early after closure (n=13), another 6 patients became migraine-free (P=0.031). CONCLUSION: Percutaneous ASD closure was not related to a significant decrease in overall migraine prevalence. However, new-onset and persistent migraine early after closure disappeared.

Complications and mid-term outcome after percutaneous patent foramen ovale closure in patients with cryptogenic stroke.

BACKGROUND: Percutaneous patent foramen ovale (PFO) closure seems to reduce the risk of recurrent thromboembolism. We report the safety and efficacy of percutaneous PFO closure in our centre. METHODS: All patients, >16 years of age, who underwent a percutaneous PFO closure in our centre were included. Reoccurrence of stroke, transient ischaemic attack (TIA) and peripheral thromboembolism were assessed. Periprocedural and midterm complications are reported. RESULTS: Eighty-three consecutive patients (mean age 49+/-13 years) were included. Indications for PFO closure were cryptogenic stroke (59.0%), TIA (33.7%), peripheral embolism (2.4%) and other (4.8%). For PFO closure, a Cardioseal/Starflex device was used in 63 patients and an Amplatzer PFO occluder device in 20 patients. Stroke recurred in 1.2%, TIA in 3.6%, peripheral embolism in 0% during a mean follow-up of 1.9+/-1.2 years. Major periprocedural complications occurred in 1.2%. The mid-term complication rate was 2.4% and only consisted of minor complications. During follow-up, a residual right-to-left shunt was present in 5.7% of the patients. No significant difference in outcome, complications or residual shunting could be documented between the two device types. CONCLUSION: In our centre, the percutaneous closure of a PFO seems to be a safe and effective procedure to prevent recurrence of paradoxical thrombo-embolic events. (Neth Heart J 2008;16:332-6.).

Patent foramen ovale and migraine.

Migraine is a common neurological disorder with a great impact on the quality of life and social activities. The patent foramen ovale (PFO) is an intra-atrial right-to-left shunt with a prevalence of 25% in the general population. An increased prevalence is found in patients with migraine, especially in migraine with aura. Percutaneous PFO closure might decrease the prevalence of migraine. However, most of these observational studies were retrospective without a randomized design and the results need to be interpreted with caution. In this review we describe the association between PFO and migraine and the different pathophysiological hypotheses, which have been proposed to explain this relationship.