Pulmonary arteriovenous malformations in patients with previous brain abscess: a cross-sectional population-based study.

BACKGROUND AND PURPOSE: Pulmonary arteriovenous malformations (PAVMs) may cause recurrent brain abscess. The primary aim was to determine the prevalence of PAVM amongst survivors of brain abscess. The proportion with cardiac right-to-left shunts was also assessed post hoc. METHODS: This was a cross-sectional population-based study of adult (≥18 years) survivors of cryptogenic bacterial brain abscess in Denmark from 2007 through 2016. Patients were invited for bubble-echocardiography to detect vascular right-to-left shunting and, if abnormal, subsequent computed tomography thorax for diagnosis of PAVM. Data are presented as n/N (%) or median with interquartile range (IQR). RESULTS: Study participation was accepted by 47/157 (30%) eligible patients amongst whom two did not appear for scheduled bubble-echocardiography. The median age of participants was 54 years (IQR 45-62) and 19/57 (33%) were females compared with 59 years (IQR 48-68, p = 0.05) and 41/85 females (48%, p = 0.22) in non-participants. Bubble-echocardiography was suggestive of shunt in 10/45 (22%) participants and PAVM was subsequently confirmed by computed tomography in one patient with grade 1 shunting. The corresponding prevalence of PAVM was 2% (95% confidence interval 0.06-11.8) amongst all examined participants. Another 9/45 (20%) were diagnosed with patent in persistent foramen ovale (n = 8) or atrial septum defect (n = 1), which is comparable with the overall prevalence of 25% amongst adults in the Danish background population. CONCLUSIONS: Undiagnosed PAVM amongst adult survivors of cryptogenic bacterial brain abscess is rare but may be considered in select patients. The prevalence of cardiac right-to-left shunts amongst brain abscess patients corresponds to the prevalence in the general population.

Danish phase II trial using adipose tissue derived mesenchymal stromal cells for patients with ischaemic heart failure.

AIMS: Patients suffering from chronic ischaemic heart failure with reduced left ventricular ejection fraction (HFrEF) have reduced quality-of-life, repetitive hospital admissions, and reduced life expectancy. Allogeneic cell therapy is currently investigated as a potential treatment option after initially encouraging results from clinical autologous and allogeneic trials in patients with HFrEF. We aimed to investigate the allogeneic Cardiology Stem Cell Centre Adipose tissue derived mesenchymal Stromal Cell product (CSCC_ASC) as an add-on therapy in patients with chronic HFrEF. METHODS AND RESULTS: This is a Danish multi-centre double-blinded placebo-controlled phase II study with direct intra-myocardial injections of allogeneic CSCC_ASC. A total of 81 HFrEF patients were included and randomized 2:1 to CSCC_ASC or placebo injections. The inclusion criteria were reduced left ventricular ejection fraction (LVEF ≤ 45%), New York Heart Association (NYHA) class II-III despite optimal anti-congestive heart failure medication and no further revascularization options. Injections of 0.3 mL CSCC_ASC (total cell dose 100 × 106 ASCs) (n = 54) or isotonic saline (n = 27) were performed into the viable myocardium in the border zone of infarcted tissue using the NOGA Myostar® catheter (Biological Delivery System, Cordis, Johnson & Johnson, USA). The primary endpoint, left ventricular end systolic volume (LVESV), was evaluated at 6-month follow-up. The safety was measured during a 3-years follow-up period. RESULTS: Mean age was 67.0 ± 9.0 years and 66.6 ± 8.1 years in the ASC and placebo groups, respectively. LVESV was unchanged from baseline to 6-month follow-up in the ASC (125.7 ± 68.8 mL and 126.3 ± 72.5 mL, P = 0.827) and placebo (134.6 ± 45.8 mL and 135.3 ± 49.6 mL, P = 0.855) group without any differences between the groups (0.0 mL (95% CI -9.1 to 9.0 mL, P = 0.992). Neither were there significant changes in left ventricular end diastolic volume or LVEF within the two groups or between groups -5.7 mL (95% CI -16.7 to 5.3 mL, P = 0.306) and -1.7% (95% CI -4.4. to 1.0, P = 0.212), respectively). NYHA classification and 6-min walk test did not alter significantly in the two groups (P > 0.05). The quality-of-life, total symptom, and overall summary score improved significantly only in the ASC group but not between groups. There were 24 serious adverse events (SAEs) in the ASC group and 11 SAEs in the placebo group without any significant differences between the two groups at 1-year follow-up. Kaplan-Meier plot using log-rank test of combined cardiac events showed an overall mean time to event of 30 ± 2 months in the ASC group and 29 ± 2 months in the placebo group without any differences between the groups during the 3 years follow-up period (P = 0.994). CONCLUSIONS: Intramyocardial CSCC_ASC injections in patients with chronic HFrEF were safe but did not improve myocardial function or structure, nor clinical symptoms.

Randomized Trial of Surgical Left Atrial Appendage Closure: Protection Against Cerebrovascular Events.

Following open-heart surgery, atrial fibrillation and stroke occur frequently. Left atrial appendage closure added to elective open-heart surgery could reduce the risk of ischemic stroke. We aim to examine if routine closure of the left atrial appendage in patients undergoing open-heart surgery provides long-term protection against cerebrovascular events independently of atrial fibrillation history, stroke risk, and oral anticoagulation use. Long-term follow-up of patients enrolled in the prospective, randomized, open-label, blinded evaluation trial entitled left atrial appendage closure by surgery (NCT02378116). Patients were stratified by oral anticoagulation status and randomized (1:1) to left atrial appendage closure in addition to elective open-heart surgery vs standard care. The primary composite endpoint was ischemic stroke events, transient ischemic attacks, and imaging findings of silent cerebral ischemic lesions. Two neurologists blinded for treatment assignment adjudicated cerebrovascular events. In total, 186 patients (82% males) were reviewed. At baseline, mean (standard deviation (SD)) age was68 (9) years and 13.4% (n = 25/186) had been diagnosed with atrial fibrillation. Median [interquartile range (IQR)] CHA2DS2-VASc was 3 [2,4] and 25.9% (n = 48/186) were receiving oral anticoagulants. Mean follow-up was 6.2 (2.5) years. The left atrial appendage closure group experienced fewer cerebrovascular events; intention-to-treat 11 vs 19 (P = 0.033, n = 186) and per-protocol 9 vs 17 (P = 0.186, n = 141). Left atrial appendage closure as an add-on open-heart surgery, regardless of pre-surgery atrial fibrillation and oral anticoagulation status, seems safe and may reduce cerebrovascular events in long-term follow-up. More extensive randomized clinical trials investigating left atrial appendage closure in patients without atrial fibrillation and high stroke risk are warranted.

Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history: the LAACS randomized study.

BACKGROUND: Open heart surgery is associated with high occurrence of atrial fibrillation (AF), subsequently increasing the risk of post-operative ischemic stroke. Concomitant with open heart surgery, a cardiac ablation procedure is commonly performed in patients with known AF, often followed by left atrial appendage closure with surgery (LAACS). However, the protective effect of LAACS on the risk of cerebral ischemia following cardiac surgery remains controversial. We have studied whether LAACS in addition to open heart surgery protects against post-operative ischemic brain injury regardless of a previous AF diagnosis. METHODS: One hundred eighty-seven patients scheduled for open heart surgery were enrolled in a prospective, open-label clinical trial and randomized to concomitant LAACS vs. standard care. Randomization was stratified by usage of oral anticoagulation (OAC) planned to last at least 3 months after surgery. The primary endpoint was a composite of post-operative symptomatic ischemic stroke, transient ischemic attack or imaging findings of silent cerebral ischemic (SCI) lesions. RESULTS: During a mean follow-up of 3.7 years, 14 (16%) primary events occurred among patients receiving standard surgery vs. 5 (5%) in the group randomized to additional LAACS (hazard ratio 0.3; 95% CI: 0.1-0.8, p = 0.02). In per protocol analysis (n = 141), 14 (18%) primary events occurred in the control group vs. 4 (6%) in the LAACS group (hazard ratio 0.3; 95% CI: 0.1-1.0, p = 0.05). CONCLUSIONS: In a real-world setting, LAACS in addition to elective open-heart surgery was associated with lower risk of post-operative ischemic brain injury. The protective effect was not conditional on AF/OAC status at baseline. TRIAL REGISTRATION: LAACS study, clinicaltrials.gov NCT02378116 , March 4th 2015, retrospectively registered.

Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial.

AIMS: To determine the effect of the glucagon-like peptide-1 analogue liraglutide on left ventricular function in chronic heart failure patients with and without type 2 diabetes. METHODS AND RESULTS: LIVE was an investigator-initiated, randomised, double-blinded, placebo-controlled multicentre trial. Patients (n = 241) with reduced left ventricular ejection fraction (LVEF ≤45%) were recruited (February 2012 to August 2015). Patients were clinically stable and on optimal heart failure treatment. Intervention was liraglutide 1.8 mg once daily or matching placebo for 24 weeks. The LVEF was similar at baseline in the liraglutide and the placebo group (33.7 ± 7.6% vs. 35.4 ± 9.4%). Change in LVEF did not differ between the liraglutide and the placebo group; mean difference (95% confidence interval) was -0.8% (-2.1, 0.5; P = 0.24). Heart rate increased with liraglutide [mean difference: 7 b.p.m. (5, 9), P < 0.0001]. Serious cardiac events were seen in 12 (10%) patients treated with liraglutide compared with 3 (3%) patients in the placebo group (P = 0.04). CONCLUSION: Liraglutide did not affect left ventricular systolic function compared with placebo in stable chronic heart failure patients with and without diabetes. Treatment with liraglutide was associated with an increase in heart rate and more serious cardiac adverse events, and this raises some concern with respect to the use of liraglutide in patients with chronic heart failure and reduced left ventricular function. More data on the safety of liraglutide in different subgroups of heart failure patients are needed.

Impact of extracorporeal blood flow rate on blood pressure, pulse rate and cardiac output during haemodialysis.

BACKGROUND: If blood pressure (BP) falls during haemodialysis (HD) [intradialytic hypotension (IDH)] a common clinical practice is to reduce the extracorporeal blood flow rate (EBFR). Consequently the efficacy of the HD (Kt/V) is reduced. However, only very limited knowledge on the effect of reducing EBFR on BP exists and data are conflicting. The aim of this study was to evaluate the effect and the potential mechanism(s) involved by investigating the impact of changes in EBFR on BP, pulse rate (PR) and cardiac output (CO) in HD patients with arteriovenous-fistulas (AV-fistulas). METHODS: We performed a randomized, crossover trial in 22 haemodynamically stable HD patients with AV-fistula. After a conventional HD session each patient was examined during EBFR of 200, 300 and 400 mL/min in random order. After 15 min when steady state was achieved CO, BP and PR were measured at each EFBR, respectively. RESULTS: Mean (SD) age was 71 (11) years. Systolic BP was significantly higher at an EBFR of 200 mL/min as compared with 300 mL/min [133 (23) versus 128 (24) mmHg; P < 0.05], but not as compared with 400 mL/min [133 (23) versus 130 (19) mmHg; P = 0.20]. At EBFR of 200, 300 and 400 mL/min diastolic BP, mean arterial pressure, PR and CO remained unchanged. CONCLUSION: Our study does not show any consistent trend in BP changes by a reduction in EBFR. Reduction in EBFR if BP falls during IDH is thus not supported. However, none of the patients experienced IDH. Further studies are required to evaluate the impact of changes in EBFR on BP during IDH.

A protocol for a randomised, double-blind, placebo-controlled study of the effect of LIraglutide on left VEntricular function in chronic heart failure patients with and without type 2 diabetes (The LIVE Study).

INTRODUCTION: Heart failure is one of the most common cardiovascular complications of diabetes and the most disabling and deadly complication too. Many antidiabetic agents have been associated with increased morbidity and mortality in a subset of patients with chronic heart failure (CHF); thus, new treatment modalities are warranted. Interestingly, a beneficial effect of the incretin hormone, GLP-1, on cardiac function has been suggested in patients with diabetes and patients without diabetes. Liraglutide (Victoza) is a GLP-1 analogue developed for the treatment of type 2 diabetes (T2D); however, its impact on cardiac function has not previously been investigated in patients with CHF. This prompted us to investigate whether liraglutide treatment for 24 weeks improves left ventricular ejection fraction (LVEF) in patients with CHF with and without T2D compared with placebo treatment. METHODS AND ANALYSIS: An investigator-initiated, multicentre, randomised, double-blind, parallel, placebo-controlled intervention trial. In total, 240 patients with CHF (with and without T2D) with LVEF≤45% will be randomised to either subcutaneous injection of liraglutide 1.8 mg or matching placebo once daily for 24 weeks. The effect of liraglutide on left ventricular function will be evaluated by advanced echocardiography, including three-dimensional contrast echocardiography. ETHICS AND DISSEMINATION: The study will be performed and monitored according to the Good Clinical Practice-International Conference on Harmonisation (GCP-ICH) regulations and conducted according to the principles of the Helsinki Declaration. The Danish Medicines Agency, the local Research Ethics Committee and the Danish Data Protection Agency have approved the study. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01472640.

Plasma YKL-40 is elevated in patients with recurrent atrial fibrillation after catheter ablation.

AIM: To study plasma YKL-40 in patients with atrial fibrillation (AF) treated with radiofrequency (RF) catheter ablation and to assess the predictive role of plasma YKL-40 and its changes after restoration of sinus rhythm (SR). METHODS: Forty-six patients (mean age 55 years, range 31-81) with paroxysmal/persistent AF were treated with RF catheter ablation; Holter monitoring for 14 days was performed before ablation and after 3 months. Recurrent symptomatic AF or atrial tachycardia >10 min was considered failure, and the patients were offered a second ablation session. YKL-40 was determined in plasma samples taken prior to ablation and at follow-up visits up to 12 months after ablation. RESULTS: After a maximum of two ablations, 19 patients (41%) had SR without recurrence of AF after 12 months. The patients with no recurrence of AF had significantly lower baseline plasma levels of YKL-40 prior to ablation compared to patients with recurrence of AF (31 vs. 62 microg/l, P = 0.029). Plasma YKL-40 was not an independent predictor of recurrence of AF after ablation. No significant changes in plasma YKL-40 levels were seen from baseline to follow-up at 12 months. CONCLUSION: In patients with paroxysmal or persistent AF treated with catheter ablation, high plasma YKL-40 before ablation is associated with recurrence of AF.

Increased NT-pro-B-type natriuretic peptide independently predicts outcome following catheter ablation of atrial fibrillation.

AIMS: To investigate whether NT-proBNP before ablation treatment and after exercise testing has predictive information regarding the clinical outcome following pulmonary vein isolation in patients with atrial fibrillation (AF). METHODS: NT-proBNP analysis were obtained before the ablation (before and after exercise test), and repeated at 1, 3, and 12 months after the final procedure. RESULTS: A total of 51 patients were included. At study entry, the median NT-proBNP concentration was 14.0 pmol/L (quartiles: 8.0 and 27.0). After the exercise test, the mean NT-proBNP value increased from 13.0 pmol/L (quartiles: 7.5 and 26.0) to 15.0 pmol/L (quartiles: 9.0 and 34.0), p < 0.001. Following a maximum of two ablations, 22 patients were free of AF while 29 patients experienced recurrent AF. In patients with successful ablation, the mean NT-proBNP concentration at baseline was 10.0 pmol/L (quartiles: 7.0 and 22.2) compared to 22.0 pmol/L (quartiles: 12.0 and 34.5) in patients with ablation failure, p = 0.02. With respect to exercise testing, a trend towards a higher increases during exercise were seen in patients with recurrent AF compared to patients without: 2.0 pmol/L (quartiles 1.9 and 7.0) vs. 1.5 pmol/L (quartiles 0 and 3.0), p = 0.07. A baseline NT-proBNP concentration >15.0 pmol/L was found to be an independent predictor of ablation failure. CONCLUSION: A significantly lower NT-proBNP concentration at baseline and a trend towards a diminished increase during exercise was seen in patients successfully ablated for AF compared to patients with recurrent AF. A baseline NT-proBNP concentration

Prognostic impact of hs-CRP and IL-6 in patients undergoing radiofrequency catheter ablation for atrial fibrillation.

AIM: The aim of this study was to assess the predictive value of inflammatory markers in patients with paroxysmal/persistent atrial fibrillation (AF) treated with radiofrequency (RF) catheter ablation. METHODS: Forty-six consecutive patients, mean age 55 years (range 31 - 81 yrs), with paroxysmal or persistent AF were treated with either segmental or circumferential pulmonary vein isolation ablation technique. All patients presented with sinus rhythm on inclusion. Holter monitoring lasting at least 14 days was performed before ablation and after 3 months. Recurrent symptomatic AF or atrial tachycardia >10 minutes was considered failure and patients were offered a second ablation session. Interleukin-6 and high-sensitivity C-reactive protein were measured prior to ablation and at follow-up visits. RESULTS: After a maximum of two ablations, 19 patients (41%) had SR without recurrence of AF after 12 months. Patients in SR had significantly lower left atrium diameter (p = 0.007) and lower values of both IL-6 (p = 0.007) and hs-CRP (p = 0.018) at baseline before ablation. IL-6 concentration prior to ablation was an independent predictor of recurrent AF (p = 0.027). CONCLUSION: In patients with a history of paroxysmal or persistent AF treated with RF catheter ablation, elevated levels of IL-6 and hs-CRP before ablation are independent predictors of recurrence of AF.

The effectiveness of a high output/short duration radiofrequency current application technique in segmental pulmonary vein isolation for atrial fibrillation.

AIMS: Segmental pulmonary vein (PV) isolation by radiofrequency (RF) catheter ablation has become a curative therapy for atrial fibrillation (AF). However, the long procedure time limits the wide application of this procedure. The aim of the current study was to compare a novel ablation technique with a high power output and short application time vs. a conventional technique using a low power output and long application time. METHODS AND RESULTS: The study included 90 consecutive patients (age 53+/-10 years; 66 men). Segmental PV isolation was performed by irrigated RF catheter ablation in both groups. In the conventional group (Group 1, 45 patients), the power output was limited to 30 W with a target temperature of 50 degrees C and an RF preset duration of 120 s. In the novel group (Group 2, 45 patients), the maximum power output was preset to 45 W, with a target temperature of 55 degrees C and duration of 20 s. In Group 2, a significant reduction in the PV isolation time (127+/-57 vs. 94+/-33 min, P<0.02), mean fluoroscopy time (73+/-23 vs. 55+/-16 min, P<0.001), and radiation dose was observed. According to the application time and number, Group 2 showed a reduction in RF application time, but a higher number of RF applications were required for creation of complete PV isolation. During a mean follow-up of 15+/-7 months, a total of 74% of patients in Group 1 and 76% of patients in Group 2 demonstrated stable SR. CONCLUSION: Segmental PV isolation using a high power output and short application time is safe and effective in PV isolation in patients with AF. This technique can significantly reduce the procedure and fluoroscopy time compared with a low-power output technique.

Recurrence of pulmonary vein conduction and atrial fibrillation after pulmonary vein isolation for atrial fibrillation: a randomized trial of the ostial versus the extraostial ablation strategy.

BACKGROUND: Both segmental ostial and circumferential extraostial pulmonary vein (PV) isolation have been proven effective in the treatment of atrial fibrillation (AF). However, the recurrence of AF and PV conduction after the 2 ablation strategies has never been compared in a randomized study. METHODS: A total of 100 consecutive patients (age 56 +/- 10; 71 men) with symptomatic AF (paroxysmal, 51; persistent, 49) were randomized to segmental ostial (n = 54) or circumferential extraostial (n = 46) PV isolation. A circular catheter positioned at the ostium of each target PV guided the ostial PV isolation. Extraostial PV isolation was performed by encircling the paired left and right PVs, respectively, guided by an electroanatomic mapping system. RESULTS: A total of 84% of the patients had recurrent AF after the first PV isolation procedure, showing 72% with AF and 12% with organized left atrial tachycardia. In patients undergoing reablation, all but 2 patients had recurrence of left atrium PV conduction (>95%). During a mean follow-up of 12 months without antiarrhythmic medication, 57% of patients who underwent extraostial PV isolation were free of arrhythmia symptoms compared with 31% of patients who underwent ostial PV isolation (P < .05). This difference in success rate between the 2 ablation strategies was mainly seen in patients known with persistent AF (52% and 15%, respectively; P = .02) as opposed to patients with paroxysmal AF (65% and 46%, respectively; P = .26). CONCLUSIONS: Overall, the more proximal, extraostial PV isolation was found to be superior to ostial PV isolation, especially in patients known with persistent AF. A high recurrence rate of 84% after a single complete PV isolation procedure was seen. At reablation, more than 95% had recurrence of left atrium PV conduction regardless of the procedure used, supporting the idea that complete PV isolation seems essential to prevent arrhythmia recurrences.

Atrial secretion of B-type natriuretic peptide.

In the normal heart, the endocrine capacity resides in the atria. Atrial myocytes express and secrete natriuretic hormones that regulate fluid homeostasis and blood pressure. But in ventricular disease, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) gene expression is also activated in ventricular myocytes. Plasma concentrations of natriuretic peptides and their biosynthetic precursors are accordingly increased in patients with marked ventricular dysfunction. In contrast, atrial peptide secretion in ventricular disease has received less attention, and our present understanding of the endocrine atria during ventricular dysfunction is still scarce. Although ventricular disease and increased circulating concentrations are associated, it does not entail that the ventricle is the sole or even the main source in all types of heart disease. Clearly, the endocrine atria are also active in heart failure. Plasma measurement of cardiac natriuretic peptides and their molecular precursors can perhaps help us to discriminate when, where and how.

Increased resting heart rate following radiofrequency catheter ablation for atrial fibrillation.

AIM: Sinus tachycardia has been observed following radiofrequency (RF) catheter ablation for various kinds of supraventricular tachycardia. This study is aimed at determining the occurrence of changes in sinus-rhythm heart rate (HR) after pulmonary vein (PV) isolation in patients with paroxysmal/persistent atrial fibrillation (AF), prospectively. METHODS: Patients with a history of AF underwent segmental or circumferential isolation of the PVs. A total of 62 consecutive patients, mean age 55 +/- 10, was included. Clinical evaluation was performed before and one, three, six, nine, and 12 months following the procedure. RESULTS: Following PV isolation, the mean HR significantly increased from 58 +/- 10 bpm at baseline to 67 +/- 12 bpm at one month, 71 +/- 13 bpm at three months, 69 +/- 12 bpm at six months, 69 +/- 13 at nine months, and 70 +/- 13 at 12 months follow-up. The ablation success significantly correlated with the increase in HR at one month follow-up. In three patients the mean HR increased > 25 bpm resulting in symptoms necessitating therapy with rate-controlling drugs. CONCLUSION: PV isolation in patients with AF may result in increased HR, which positively correlated with the ablation success. This change does not seem to resolve spontaneously after a follow-up of 12 months. Approximately 5% of patients may develop symptoms due to an increased HR, necessitating treatment with rate-controlling drugs.

Acute fatal pulmonary vein occlusion after catheter ablation of atrial fibrillation.

BACKGROUND: In treatment of atrial fibrillation (AF) catheter radiofrequency isolation of the pulmonary veins (PVs) has proved to be highly successful. There have been several case reports regarding PV stenosis, however none of these have reported a fatal outcome. METHODS AND RESULTS: A 31-year-old man was referred to us for treatment of complications related to catheter ablation. According to the documentation from the hospital, the patient underwent segmental ostial PV isolation for treatment of AF. A few hours after the procedure, the patient developed dyspnoea, hemoptysis, and a high fever. The patient was first diagnosed as having pneumonia but five days later transesophageal echocardiography and pulmonal angiography revealed total occlusion of the left superior and inferior PVs. When we received the patient he underwent open-heart surgery, which showed thrombi in the orifices of the left sided PVs protruding into the left atrium. In each of the left sided PVs severe stenosis was seen in the bifurcation area. Thrombus material was removed followed by placement of two stents in each of the left sided pulmonary veins at the first bifurcations. However, the patient died 14 days after the ablation procedure. Selective autopsy of the left lung revealed diffuse alveolar damage, disseminated intravascular coagulation, multiple thrombi formation, and haemorrhagic infarctions. CONCLUSIONS: PV stenosis may occur very early after the ablation procedure. Delayed diagnosis can be fatal. The early stenosis may result in thrombus formation in the left atrium and PVs and in this case surgery should be considered.