Increased epicardial adipose tissue is associated with left atrial mechanical dysfunction in patients with heart failure with mildly reduced and preserved ejection fraction.

INTRODUCTION: Heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF) is often accompanied by atrial dysfunction. It has been suggested that specific ectopic fat depots, such as epicardial adipose tissue (EAT), may directly influence the myocardial cells and, therefore, be involved in the pathophysiology of atrial mechanical dysfunction. In this study, we aimed to investigate the association between EAT and left atrial (LA) mechanical dysfunction. METHODS AND RESULTS: In total, 82 patients with symptomatic HF and left ventricular ejection fraction > 40% were prospectively enrolled. All patients underwent CMR while in sinus rhythm. LA mechanical dysfunction was defined as the presence of LA end-systolic volume index > 52 mL/m2 and LA reservoir strain < 23%. EAT volume was indexed for body surface area. Mean age was 69 ± 10 years, 42 (51%) were women and mean body mass index (BMI) was 29 ± 6 kg/m2. Mean LVEF was 55 ± 9% and 34 (41%) patients had LA mechanical dysfunction. In patients with LA mechanical dysfunction, the EAT volume was significantly higher than in patients without LA mechanical dysfunction (90 vs 105 mL/m2, p = 0.02) while BMI was similar. In multivariable logistic regression analyses, increased EAT remained significantly associated with LA mechanical dysfunction (OR 1.31, 95% CI 1.03-1.66, p = 0.03). CONCLUSION: Increased EAT was associated with LA mechanical dysfunction in patients with HFmrEF and HFpEF. Further research is needed to elucidate the exact mechanisms that underlie this association.

Pulmonary artery pressure monitoring in chronic heart failure: effects across clinically relevant subgroups in the MONITOR-HF trial.

BACKGROUND AND AIMS: In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. METHODS: The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronisation therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life, clinical, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. RESULTS: The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were nonsignificant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = 0.03; adjusted Pinteraction = 0.33) and diabetics (Pinteraction = 0.01; adjusted Pinteraction = 0.06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. CONCLUSIONS: This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients.

Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium.

BACKGROUND: Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF. METHOD AND RESULTS: Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: <65; 65-75; and >75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94-0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata. CONCLUSIONS: For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.

Increased plasma levels of NT-proBNP, Troponin T and GDF-15 are driven by persistent AF and associated comorbidities: Data from the AF-RISK study.

Atrial fibrillation (AF) is a progressive disease, and early recognition and management may reflect an important strategy to reduce its disease burden. In this study, we evaluated plasma levels of three biomarkers - N-terminal pro-brain natriuretic peptide (NTproBNP), Troponin-T, and growth differentiation factor-15 (GDF-15) - in patients with paroxysmal AF (pAF) (≤7 days of continuous AF, n = 323) and persistent AF ((AF duration > 7 days and < 1 year, n = 84) using patients from AF RISK study (NCT01510210). In this AF-RISK sub-study, patients with persistent AF experienced more symptoms (higher European Heart Rhythm Association class (p < 0.001)), had a higher comorbidity burden (p < 0.001), and had more unfavorable echocardiographic parameters (p < 0.001). All three biomarker levels were significantly higher in patients with persistent AF as compared to those with pAF (p < 0.001). Multivariate linear regression analyses showed that age (beta-coefficient for NTproBNP: 0.21; GDF-15: 0.41; Troponin-T: 0.23) and CHA2DS2-VASc (beta-coefficient for NTproBNP: 0.20; GDF-15: 0.25; Troponin-T: 0.27) were determinants of all three biomarkers, and that persistent AF determined NTproBNP (beta-coefficient: 0.34), but not Troponin-T and GDF-15. More detailed analysis of CHA2DS2-VASc score showed that for all three biomarkers age, coronary artery disease and heart failure were determinants of plasma biomarkers levels, whereas sex determined NTproBNP and Troponin T, and hypertension determined NTproBNP and GDF15. Overall, this study therefore suggests that in AF, Troponin T and GDF15, and especially NTproBNP could be used to detect those patients with more persistent form of AF that may warrant more aggressive treatment of AF and concomitant comorbidities. Future studies, however, are essential to evaluate if more aggressive AF treatment and risk factor management will reduce disease progression and holds a novel therapeutic intervention to reduce the burden of AF.

Heart rate increase and inappropriate sinus tachycardia after cryoballoon pulmonary vein isolation for atrial fibrillation.

BACKGROUND: Cryoballoon pulmonary vein isolation (PVI) is a common therapy for atrial fibrillation (AF). While moderately increased sinus rhythm heart rate (HR) after PVI has been observed, inappropriate sinus tachycardia (IST) is a rare phenomenon. We aimed to investigate the prevalence and natural history of an abnormal sinus HR response after cryoballoon PVI. METHODS: We included 169/646 (26.2%) patients with AF undergoing PVI with available Holter recordings before and 3, 6 and 12 months after the procedure. Patients with AF on Holter monitoring were excluded. Mean HR increase ≥ 20 bpm or an IST-like pattern (mean HR > 90 bpm or > 80 bpm when beta-blocking agents were used) following PVI was categorised as abnormal sinus HR response. RESULTS: Following PVI, mean HR ± standard deviation increased in the entire group from 63.5 ± 8.4 to 69.1 ± 9.9 bpm at 3 months (p < 0.001), and to 71.9 ± 9.4 bpm at 6 months (p < 0.001). At 12 months, mean HR was 71.2 ± 10.1 bpm (p < 0.001). Only 7/169 patients (4.1%) met criteria for abnormal sinus HR response: mean HR was 61.9 ± 10.6 bpm (pre-ablation), 84.6 ± 9.8 bpm (3 months), 80.1 ± 6.5 bpm (6 months) and 76.3 ± 10.1 bpm (12 months). Even at 12 months, mean HR was significantly different from that pre-ablation in this group (p = 0.033). However, in patients meeting IST-like pattern criteria, mean HR at 12 months was no longer significantly different from that pre-ablation. CONCLUSION: Few patients had an abnormal sinus HR response after PVI. Peak HR was observed 3 months after PVI, but HR was still significantly increased 12 months post-ablation compared with pre-ablation. An IST-like pattern was rarely observed. In these patients, HR decreased to pre-ablation values within a year.

Gut-microbe derived TMAO and its association with more progressed forms of AF: Results from the AF-RISK study.

INTRODUCTION: The importance of gut microbiome in cardiovascular disease has been increasingly recognized. Trimethylamine N-oxide (TMAO) is a gut microbe-derived metabolite that is associated with cardiovascular disease, including atrial fibrillation (AF). The role of TMAO in clinical AF progression however remains unknown. METHODS AND RESULTS: In this study we measured TMAO and its precursor (betaine, choline, and L- carnitine) levels in 78 patients using plasma samples from patients that participated in the AF-RISK study. 56 patients suffered from paroxysmal AF and 22 had a short history of persistent AF. TMAO levels were significantly higher in patients with persistent AF, as compared to those with paroxysmal AF (median [IQR] 5.65 [4.7-9.6] m/z versus 4.31 [3.2-6.2] m/z, p < 0.05), while precursor levels did not differ. In univariate analysis, we observed that for every unit increase in TMAO, the odds for having persistent AF increased with 0.44 [0.14-0.73], p < 0.01. Conclusion: These results suggest that higher levels of TMAO are associated with more progressed forms of AF. We therefore hypothesize that increased TMAO levels may reflect disease progression in humans. Larger studies are required to validate these preliminary findings.Trial Registration number: Clinicaltrials.gov NCT01510210.

Downgrade of cardiac defibrillator devices to pacemakers in elderly heart failure patients: clinical considerations and the importance of shared decision-making.

Implantable cardioverter defibrillators are implanted on a large scale in patients with heart failure (HF) for the prevention of sudden cardiac death. There are different scenarios in which defibrillator therapy is no longer desired or indicated, and this is occurring increasingly in elderly patients. Usually device therapy is continued until the device has reached battery depletion. At that time, the decision needs to be made to either replace it or to downgrade to a pacing-only device. This decision is dependent on many factors, including the vitality of the patient and his/her preferences, but may also be influenced by changes in recommendations in guidelines. In the last few years, there has been an increased awareness that discussions around these decisions are important and useful. Advanced care planning and shared decision-making have become important and are increasingly recognised as such. In this short review we describe six elderly patients with HF, in whose cases we discussed these issues, and we aim to provide some scientific and ethical rationale for clinical decision-making in this context. Current guidelines advocate the discussion of end-of-life options at the time of device implantation, and physicians should realise that their choices influence patients' options in this critical phase of their illness.

Genetically-determined body mass index and the risk of atrial fibrillation progression in men and women.

AIMS: Limited causal evidence is available on the relationship between body mass index (BMI) and atrial fibrillation (AF) progression. Sex differences have been noted and may be relevant for AF progression. We investigated the association between the BMI Genetic Risk Score (GRS) and AF progression in men and women of the Groningen Genetic Atrial Fibrillation (GGAF) cohort. METHODS AND RESULTS: The GGAF cohort (n = 2207) is a composite of 5 prospective cohorts with individuals of European ancestry. AF patients with genetic information, with at least 12 months follow-up and AF progression data were included. AF progression was defined as progression from paroxysmal to persistent/permanent AF, or persistent to permanent AF. A BMI GRS was constructed of genetic variants associated with BMI. Univariate and multivariate Cox proportional hazard regression analyses were performed in the total population and in men and women, separately. During a median follow-up of 34 [interquartile range 19-48] months 630 AF patients (mean age 62±11, 36% women, BMI of 28±5) were analyzed, and men and women developed similar AF progression rates (respectively 6.5% versus 6.1%). The BMI GRS was not associated with AF progression either as a continuous variable or in tertiles in the overall population. However, the BMI GRS was associated with the tertile of the highest BMI GRS in women (n = 225), also after multivariable adjustments of clinical risk factors (Hazard ratio 2.611 (95% confidence interval 1.151-5.924) p = 0.022). CONCLUSIONS: Genetically-determined BMI is only associated with women at risk of AF progression. The results may be supporting evidence for a causal link between observed BMI and AF progression in women. We emphasize the need for further investigation of genetically determined BMI and observed BMI to optimize AF management in women with increased risk for AF progression.

Reappraisal of Atrial fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V) Tissue Bank Project: study design.

BACKGROUND: The development of atrial fibrillation (AF) is a complex multifactorial process. Over the past few decades, much has been learned about the pathophysiological processes that can lead to AF from a variety of specific disease models in animals. However, our ability to recognise these disease processes in AF patients is still limited, which has contributed to the limited progress in improving rhythm control in AF. AIMS/OBJECTIVES: We believe that a better understanding and detection of the individual pathophysiological mechanisms underlying AF is a prerequisite for developing patient-tailored therapies. The RACE V Tissue Bank Project will contribute to the unravelling of the main molecular mechanisms of AF by studying histology and genome-wide RNA expression profiles and combining this information with detailed phenotyping of patients undergoing cardiac surgery. METHODS: As more and more evidence suggests that AF may occur not only during the first days but also during the months and years after surgery, we will systematically study the incidence of AF during the first years after cardiac surgery in patients with or without a history of AF. Both the overall AF burden as well as the pattern of AF episodes will be studied. Lastly, we will study the association between the major molecular mechanisms and the clinical presentation of the patients, including the incidence and pattern of AF during the follow-up period. CONCLUSION: The RACE V Tissue Bank Project combines deep phenotyping of patients undergoing cardiac surgery, including rhythm follow-up, analysis of molecular mechanisms, histological analysis and genome-wide RNA sequencing. This approach will provide detailed insights into the main pathological alterations associated with AF in atrial tissue and thereby contribute to the development of individualised, mechanistically informed patient-tailored treatment for AF.

Therapeutic options for patients with advanced atrial fibrillation: from lifestyle and medication to catheter and surgical ablation.

Atrial fibrillation (AF) is part of a vicious cycle that includes multiple cardiovascular risk factors and comorbidity which can promote atrial remodelling and AF progression. Most AF-related risk factors-hypertension, diabetes, sleep apnoea, obesity and sedentary lifestyle-are in essence modifiable which may prevent AF development. Treatment of associated cardiovascular conditions may prevent both symptoms and future cardiovascular events. For advanced forms of symptomatic AF refractory to lifestyle management and optimal medication, invasive ablation therapies have become a cornerstone. Although electrical trigger isolation from the pulmonary veins is reasonably effective and safe, more potent energy sources including high output-short duration radiofrequency, ultra-low cryo-energy, and electroporation, as well as more sophisticated arrays, balloons, and lattice-tipped catheter tools, are on their way to eliminate existing pitfalls and simplify the procedure. Electroanatomical navigation and mapping systems are becoming available to provide real-time information on ablation lesion quality and the critical pathways of AF in the individual patient to guide more extensive ablation strategies that may enhance long-term outcome for freedom of advanced AF. Surgical techniques, either stand-alone or concomitant to structural cardiac repair, hybrid, or convergent, with novel less invasive access options are developing and can be helpful in situations unsuitable for catheter ablation.

Complex clinical scenarios with the use of direct oral anticoagulants in patients with atrial fibrillation: a multidisciplinary expert advisory board.

The risk of developing atrial fibrillation (AF) and the risk of stroke both increase with advancing age. As such, many individuals have, or will develop, an indication for oral anticoagulation to reduce the risk of stroke. Currently, a large number of anticoagulants are available, including vitamin K antagonists, direct thrombin or factor Xa inhibitors (the last two also referred to as direct oral anticoagulants or DOACs), and different dosages are available. Of the DOACs, rivaroxaban can be obtained in the most different doses: 2.5 mg, 5 mg, 15 mg and 20 mg. Many patients develop co-morbidities and/or undergo procedures that may require the temporary combination of anticoagulation with antiplatelet therapy. In daily practice, clinicians encounter complex scenarios that are not always described in the treatment guidelines, and clear recommendations are lacking. Here, we report the outcomes of a multidisciplinary advisory board meeting, held in Utrecht (The Netherlands) on 3 June 2019, on decision making in complex clinical situations regarding the use of DOACs. The advisory board consisted of Dutch cardiovascular specialists: (interventional) cardiologist, internist, neurologist, vascular surgeon and general practitioners invited according to personal title and specific field of expertise.

A randomised comparison of the effect of haemodynamic monitoring with CardioMEMS in addition to standard care on quality of life and hospitalisations in patients with chronic heart failure : Design and rationale of the MONITOR HF multicentre randomised clinical trial.

BACKGROUND: Assessing haemodynamic congestion based on filling pressures instead of clinical congestion can be a way to further improve quality of life (QoL) and clinical outcome by intervening before symptoms or weight gain occur in heart failure (HF) patients. The clinical efficacy of remote monitoring of pulmonary artery (PA) pressures (CardioMEMS; Abbott Inc., Atlanta, GA, USA) has been demonstrated in the USA. Currently, the PA sensor is not reimbursed in the European Union as its benefit when applied in addition to standard HF care is unknown in Western European countries, including the Netherlands. AIMS: To demonstrate the efficacy and cost-effectiveness of haemodynamic PA monitoring in addition to contemporary standard HF care in a high-quality Western European health care system. METHODS: The current study is a prospective, multi-centre, randomised clinical trial in 340 patients with chronic HF (New York Heart Association functional class III) randomised to HF care including remote monitoring with the CardioMEMS PA sensor or standard HF care alone. Eligible patients have at least one hospitalisation for HF in 12 months before enrolment and will be randomised in a 1:1 ratio. Minimum follow-up will be 1 year. The primary endpoint is the change in QoL as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Secondary endpoints are the number of HF hospital admissions and changes in health status assessed by EQ-5D-5L questionnaire including health care utilisation and formal cost-effectiveness analysis. CONCLUSION: The MONITOR HF trial will evaluate the efficacy and cost-effectiveness of haemodynamic monitoring by CardioMEMS in addition to standard HF care in patients with chronic HF. Clinical Trial Registration number NTR7672.

Enhancing cardiovascular artificial intelligence (AI) research in the Netherlands: CVON-AI consortium.

BACKGROUND: Machine learning (ML) allows the exploration and progressive improvement of very complex high-dimensional data patterns that can be utilised to optimise specific classification and prediction tasks, outperforming traditional statistical approaches. An enormous acceleration of ready-to-use tools and artificial intelligence (AI) applications, shaped by the emergence, refinement, and application of powerful ML algorithms in several areas of knowledge, is ongoing. Although such progress has begun to permeate the medical sciences and clinical medicine, implementation in cardiovascular medicine and research is still in its infancy. OBJECTIVES: To lay out the theoretical framework, purpose, and structure of a novel AI consortium. METHODS: We have established a new Dutch research consortium, the CVON-AI, supported by the Netherlands Heart Foundation, to catalyse and facilitate the development and utilisation of AI solutions for existing and emerging cardiovascular research initiatives and to raise AI awareness in the cardiovascular research community. CVON-AI will connect to previously established CVON consortia and apply a cloud-based AI platform to supplement their planned traditional data-analysis approach. RESULTS: A pilot experiment on the CVON-AI cloud was conducted using cardiac magnetic resonance data. It demonstrated the feasibility of the platform and documented excellent correlation between AI-generated ventricular function estimates as compared to expert manual annotations. The resulting AI solution was then integrated in a web application. CONCLUSION: CVON-AI is a new consortium meant to facilitate the implementation and raise awareness of AI in cardiovascular research in the Netherlands. CVON-AI will create an accessible cloud-based platform for cardiovascular researchers, demonstrate the clinical applicability of AI, optimise the analytical methodology of other ongoing CVON consortia, and promote AI awareness through education and training.

Hybrid atrial fibrillation ablation in patients with persistent atrial fibrillation or failed catheter ablation.

BACKGROUND: Combined 'hybrid' thoracoscopic and percutaneous atrial fibrillation (AF) ablation is a strategy used to treat AF in patients with therapy-resistant symptomatic AF. We aimed to study efficacy and safety of single-stage hybrid AF ablation in patients with symptomatic persistent AF, or paroxysmal AF with failed endocardial ablation, and assess determinants of success and quality of life. METHODS: We included consecutive patients undergoing single-stage hybrid AF ablation. First, we performed epicardial ablation, via thoracoscopic access, to isolate the pulmonary veins and superior caval vein and to create a posterior left atrial box. Thereafter, isolation was assessed endocardially and complementary endocardial ablation was performed, followed by cavotricuspid isthmus ablation. Efficacy was assessed by 12-lead electrocardiography and 72-hour Holter monitoring after 3, 6 and 12 months. Recurrence was defined as AF/atrial flutter/tachycardia recorded by electrocardiography or Holter monitoring lasting >30 s during 1­year follow-up. RESULTS: Fifty patients were included, 57 ± 9 years, 38 (76%) men, 5 (10%) paroxysmal, 34 (68%) persistent and 11 (22%) long-standing persistent AF. At 1­year 38 (76%) maintained sinus rhythm off antiarrhythmic drugs. Majority of recurrences were atrial flutter (9/12 patients). Success was associated with type of AF (p = 0.039). Patients with paroxysmal AF had highest success, patients with longstanding persistent AF had lowest success. Seven (14%) patients had procedure-related complications. Quality of life improved after ablation in patients who maintained sinus rhythm. CONCLUSION: Success of single-stage hybrid AF ablation was 76% off antiarrhythmic drugs, being associated with type of AF. Quality of life improved significantly, Procedure-related complications occurred in 14%.

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.

[Cardiac resynchronization therapy: who is a candidate and who is not?] / Cardiale-resynchronisatietherapie.

- Cardiac resynchronisation therapy (CRT) is a treatment for patients with impaired cardiac pump function (left ventricular ejection fraction ≤ 35%) and a wide QRS complex who, despite maximum tolerated medical therapy, remain symptomatic.- In addition to reducing symptoms, CRT can reduce hospital admissions and improve survival.- Selection of patients for CRT remains difficult. Despite the fact that predicting and influencing success of CRT has improved, ~30% of patients do not respond to the therapy.- Optimizing therapy and follow-up of patients after implantation requires a multidisciplinary approach tailored to the individual patient.- Cardiac rehabilitation with life style advices and structured exercise training maximizes patient benefit from CRT.

Tailored treatment strategies: a new approach for modern management of atrial fibrillation.

Atrial fibrillation (AF) is not benign. Cardiovascular diseases and risk factors differ importantly amongst patients. Careful phenotyping with the aim to start tailored therapy may improve outcome and quality of life. Furthermore, structural remodelling plays an important role in initiation and progression of AF. Therapies that interfere in the remodelling processes are promising because they may modify the atrial substrate. However, success is still limited probably due to variations in the underlying substrate in individual patients. The most favourable effects of lifestyle changes on success of rhythm control have been demonstrated in obese patients with AF. Differences in genotype may also play an important role. Common gene variants have been associated with recurrence of AF after electrical cardioversion, antiarrhythmic drug therapy and catheter ablation. Therefore, both phenotyping and genotyping may become useful for patient selection in the future. Beside the choice of rate or rhythm control, and type of rhythm control, prevention of complications associated with AF may also differ depending on genotype and phenotype. Efficacy of stroke prevention has been well established, but bleeding remains a clinically relevant problem. Risk stratification is still cumbersome, especially in low-risk patients and in those with a high bleeding risk. The decision whether to start anticoagulation (and if so which type of anticoagulant) or, alternatively, to implant an occlusion device of the left atrial appendage may also be improved by genotyping and phenotyping. In this review, we will summarize new insights into the roles of phenotype and genotype in generating more tailored treatment strategies in patients with AF and discuss several patient-tailored treatment options.

The diagnosis of left ventricular assist device thrombosis.

The clinical course of a patient with a left ventricular assist device is described. A total of 6 weeks after device insertion, the lactate dehydrogenase (LDH) level increased to 2801 U/l despite adding low-molecular-weight heparin to acenocoumarol and aspirin. Pump thrombosis was suspected but unconfirmed by computed tomography. Increased pump power requirement did not occur. Instituting unfractionated heparin caused a drop in the LDH level. After discontinuing heparin, the LDH levels rose to 5529 U/l whereupon pump replacement was performed. LDH levels, combined with clinical deterioration and right heart catheterisation, led to the diagnosis of pump thrombosis.

Pulmonary vein isolation of symptomatic refractory paroxysmal and persistent atrial fibrillation: A single centre and single operator experience in the Netherlands.

Aim. To investigate long-term outcome and to determine predictors of successful pulmonary vein isolation (PVI) in patients with symptomatic paroxysmal or persistent atrial fibrillation (AF) who are refractory or intolerant to antiarrhythmic drugs.Background. The treatment of AF has traditionally been pharmacological aimed at rate or rhythm control. However, rhythm control remains difficult to establish. PVI is reported to be effective in selected patient groups.Methods. Ninety-nine consecutive patients with a mean age of 54+/-10 years who had paroxysmal or persistent AF were treated in the University Medical Center Groningen. All patients underwent PVI by the same electrophysiologist. Successful PVI was defined as absence of AF on Holter or electrocardiogram (ECG), and no symptoms of AF.Results. After six months of follow-up, 60 (61%) patients were free of AF episodes, both on 96-hour Holter monitoring and on ECGs, and had no symptoms related to AF. Thirty-nine of these 60 patients (65%) were no longer treated with any class I or III antiarrhythmic drugs. Independent determinants of successful PVI were paroxysmal AF (OR 18 [3.5-93], p=0.001), and left pulmonary vein ablation time >55 minutes (OR 15 [2.7-81], p=0.002). Left atrial (parasternal view 42+/-6 vs. 40+/-5 mm, p<0.05 and apical view 61+/-9 vs. 58+/-8 mm, p<0.05) and right atrial (59+/-7 vs. 56+/-5 mm, p<0.05) sizes decreased significantly in the successfully treated patients after six months of follow-up.Conclusion. Independent determinants of a successful outcome after PVI are paroxysmal AF and a longer left atrial ablation time. (Neth Heart J 2009;17:366-72.).