Aims The role of high-intensity exercise and other emerging risk factors in lone atrial fibrillation (Ln-AF) epidemiology is still under debate. The aim of this study was to analyse the contribution of each of the emerging risk factors and the impact of physical activity dose in patients with Ln-AF.

Methods and results Patients with Ln-AF and age- and sex-matched healthy controls were included in a 2:1 prospective case–control study. We obtained clinical and anthropometric data transthoracic echocardiography, lifetime physical activity questionnaire, 24-h ambulatory blood pressure monitoring, Berlin questionnaire score, and, in patients at high risk for obstructive sleep apnoea (OSA) syndrome, a polysomnography. A total of 115 cases and 57 controls were enrolled. Conditional logistic regression analysis associated height [odds ratio (OR) 1.06 [1.01–1.11]], waist circumference (OR 1.06 [1.02–1.11]), OSA (OR 5.04 [1.44–17.45]), and 2000 or more hours of cumulative high-intensity endurance training to a higher AF risk. Our data indicated a U-shaped association between the extent of high-intensity training and AF risk. The risk of AF increased with an accumulated lifetime endurance sport activity ≥2000 h compared with sedentary individuals (OR 3.88 [1.55–9.73]). Nevertheless, a history of <2000 h of high-intensity training protected against AF when compared with sedentary individuals (OR 0.38 [0.12–0.98]).

Conclusion A history of ≥2000 h of vigorous endurance training, tall stature, abdominal obesity, and OSA are frequently encountered as risk factors in patients with Ln-AF. Fewer than 2000 total hours of high-intensity endurance training associates with reduced Ln-AF risk.

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Emerging risk factors and the dose-response relationship between physical activity and lone atrial fibrillation: a prospective case-control study.

Familial hypercholesterolaemia (FH) is an autosomal inherited disorder characterized by markedly elevated LDL-cholesterol (LDL-C) levels and an increased risk of premature atherosclerotic cardiovascular disease. Although FH is one of the most common genetic disorders, this disorder remains mostly undetected and its management is often suboptimal. High-intensity statins are standard treatment for patients with FH, but LDL-C levels in most patients treated with statin monotherapy remain above those recommended by guidelines. Combination therapy to lower LDL-C levels further-such as treatment with statins plus ezetimibe-has been successful, and combination of apheresis with high-intensity statin treatment is used in patients with homozygous FH and in those with heterozygous FH who are statin-refractory. Mipomersen, an inhibitor of apolipoprotein B-100 synthesis, and lomitapide, a microsomal triglyceride transfer protein inhibitor, reduce LDL-C levels further when added to high-intensity statin treatment in homozygous FH, but both have important adverse effects, such as increasing liver fat content. At present, PCSK9 inhibition (with alirocumab or evolocumab) is well tolerated and reduces LDL-C levels considerably in patients receiving the maximally tolerated statin treatment, and seems the most promising emerging treatment option. Nevertheless, data from outcome trials with hard end points for PCSK9 inhibitors, mipomersen, and lomitapide are still needed before these therapies become standard for patients with FH.

Management of patients with familial hypercholesterolaemia

Two-dimensional strain (2DS) is a novel method to measure strain from standard two-dimensional echocardiographic images by speckle tracking, which is less angle dependent and more reproducible than conventional Doppler-derived strain. The objective of our study was to characterize global and regional function abnormalities using 2DS and strain rate analysis in patients (pts) with pathological left ventricular hypertrophy (LVH) caused by non-obstructive hypertrophic cardiomyopathy (HCM), in top level athletes, and in healthy controls. The hypothetical question was, if 2DS might be useful as additional tool in differentiating between pathologic and physiologic hypertrophy in top-level athletes. We consecutively studied 53 subjects, 15 pts with hypertrophic cardiomyopathy (HCM), 20 competitive top-level athletes, and a control group of 18 sedentary normal subjects by standard echocardiography according to ASE guidelines. Global longitudinal strain (GLS) and regional peak systolic strain (PSS) was assessed by 2DS in the apical four-chamber-view using a dedicated software. All components of strain were significantly reduced in pts with HCM (GLS: −8.1 ± 3.8%; P < 0.001) when compared with athletes (−15.2 ± 3.6%) and control subjects (−16.0 ± 2.8%). In general, there was no significant difference between the strain values of the athletes and the control group, but in some of the segments, the strain values of the control group were significantly higher than those in the athletes. A cut-off value of GLS less than −10% for the diagnosis of pathologic hypertrophy (HCM) resulted in a sensitivity of 80.0% and a specificity of 95.0%. The combination of TDI (averaged S′, E′) and 2DS (GLS) cut-off values for the detection of pathologic LVH in HCM demonstrated a sensitivity of 100%, and a specificity of 95%. Two-dimensional strain is a new simple and rapid method to measure GLS and PSS as components of systolic strain. This technique could offer a unique approach to quantify global as well as regional systolic dysfunction, and might be used as new additional tool for the differentiation between physiologic and pathologic LVH.

Two-dimensional strain analysis of the global and regional myocardial function for the differentiation of pathologic and physiologic left ventricular hypertrophy: a study in athletes and in patients with hypertrophic cardiomyopathy.

Gender-Specific Link of Exercise Intensity With AFBackground
Despite widespread interest and extensive research, the association between different levels of physical activity (PA) and risk of atrial fibrillation (AF) is still not clearly defined. Therefore, we systematically evaluated and summarized the evidences regarding association of different intensity of PA with the risk of AF in this meta-analysis.

Methods and Results
An extensive literature search was performed on databases for studies showing association of exercise with AF risk. Twenty-two studies were identified that included 656,750 subjects. Meta-analytic estimates were derived using random-effects models and pooled odds ratio estimates were obtained. Potential sources of heterogeneity were examined in sensitivity analyses, and publication biases were estimated.

Pooled analysis of 7 studies with 93,995 participants reported high risk of incident AF with sedentary lifestyle (pooled OR 2.47 [95% CI 1.25–3.7], P = 0.005). In 3 trials, 149,048 women involved in moderate PA were 8.6% less likely to develop AF compared to women with sedentary life (OR 0.91 [95% CI 0.78–0.97], P = 0.002). Women performing intense exercise were found to have 28% lower risk of AF (OR 0.72 [95% CI 0.57–0.88], P < 0.001). The overall pooled estimate indicated a protective impact of moderate PA in men (pooled OR 0.8133 [95% CI 0.26–1.004], P = 0.06) whereas vigorous PA was associated with a significantly increased AF risk (pooled OR 3.30 [1.97–4.63], P = 0.0002).

Conclusion
Sedentary lifestyle significantly increases and moderate amount of physical activity reduces the risk of AF in both men and women. However, intense exercise has a gender-specific association with AF risk.

Differential Association of Exercise Intensity With Risk of Atrial Fibrillation in Men and Women: Evidence from a Meta-Analysis

The cardiovascular benefits of physical activity are indisputable. Nevertheless, growing evidence suggests that both atrial fibrillation and right ventricular arrhythmia can be caused by intense exercise in some individuals. Exercise-induced atrial fibrillation is most commonly diagnosed in middle-aged, otherwise healthy men who have been engaged in endurance training for >10 years, and is mediated by atrial dilatation, parasympathetic enhancement, and possibly atrial fibrosis. Cardiac ablation is evolving as a first-line tool for athletes with exercise-induced arrhythmia who are eager to remain active. The relationship between physical activity and right ventricular arrhythmia is complex and involves genetic and physical factors that, in a few athletes, eventually lead to right ventricular dilatation, followed by subsequent myocardial fibrosis and lethal ventricular arrhythmias. Sinus bradycardia and atrioventricular conduction blocks are common in athletes, most of whom remain asymptomatic, although incomplete reversibility has been shown after exercise cessation. In this Review, we summarize the evidence supporting the existence of exercise-induced arrhythmias and discuss the specific considerations for the clinical management of these patients.

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Diagnosis, pathophysiology, and management of exercise-induced arrhythmias

OBJECTIVE Cardiac adaptation to sports activity in endurance athletes is considerably different from that in power athletes. The effects of a high-level team sport like handball, one of the most popular sports in the world, performed at a younger age, on cardiac rhythm in individuals above the age of 50 have not been investigated to date. METHODS Thirty-three former top-level handball players from the first German league (6 former world champions and numerous Olympians) (57.5 +/- 5.5 y) joined our screening programme for former athletes and underwent electrocardiography, echocardiography and spiroergometry. Data were compared to 24 sedentary healthy controls. RESULTS Ten of the 33 athletes suffered from atrial fibrillation (AF). Left ventricular diameter was 53.68 +/- 4.88 mm in the athletes group and 50.58 +/- 4.12 mm in the healthy controls. Analysing the subgroups of handball players ('AF group' and 'non-AF group'), spiroergometry showed oxygen consumption at the anaerobic threshold of 27.54 +/- 6.77 ml/kg/min in the AF group and 31.24 +/- 10.33 ml/kg/min in the non-AF group (P = 0.228). Absolute left atrial diameter was 44.34 +/- 4.41 mm in the AF group (non-AF group 38.94 +/- 3.77 mm, P < 0.001) (healthy controls 37.54 +/- 4.34 mm, compared with all athletes P = 0.015). In all individuals left ventricular wall thickness was within normal limits. However, myocardial walls were thicker in the AF group (11.28 +/- 1.83 mm) than in the non-AF group (9.44 +/- 1.26 mm, P = 0.002). Athletes in the AF group (187.6 +/- 6.42 cm) were significantly taller than in the non-AF group (180.91 +/- 7.31 cm, P = 0.018). CONCLUSION Not only endurance training, but also sports activity with a relevant static component, like team handball, might predispose for AF above the age of 50. LA size, height and myocardial wall thickness seem to affect the risk of developing AF. More data in non-endurance sports are mandatory to confirm this hypothesis.

The occurrence of atrial fibrillation in former top-level handball players above the age of 50.

Introduction
Low density lipoprotein (LDL-C) apheresis is a last treatment option for hypercholesterolemic patientsresistant to conservative lipid-lowering therapy. In a retrospective analysis of 8,533 heparin-induced extra-corporeal LDL precipitation apheresis treatments (HELP), we evaluated the efficacy of LDL reduction, the rate of adverse events, and the progression of atherosclerosis.

https://link.springer.com/content/pdf/10.1007%2Fs11789-012-0048-4.pdf

HELP apheresis in hypercholesterolemia and cardiovascular disease: efficacy and adverse events after 8,500 procedures.

The key challenge in athlete's screening is the distinction between abnormal and normal which is hindered by the fact that the adaptation to sports activity in endurance athletes is different to that in power athletes. Especially cardiomyopathies provoke changes in ECG and echocardiography (echo) at an early stage when clinical symptoms are absent. ECG and echo data and their relationship to fitness peculiar to top handball players have never been described. We studied 291 male first league handball players (32 Olympians/47 national players) (25.3±4.4 years). Check up consisted of ECG, spiroergometry and echocardiography. None had T-wave inversions, 3.1% showed early repolarisation abnormalities in the precordial leads. Sokolow-Lyon voltage criterion for left ventricular hypertrophy was positive in 19.3%. Spiroergometry showed a maximum oxygen uptake (peakVO₂) of 50.3±7.7 ml/min/kg body weight. LVmass was increased in comparison to normal values. There was a correlation between peakVO₂ and LVindex (p<0.001, r=0.341), (LVmass/peak VO₂ p=0.053, r=0.125). A relationship between cardiac dimensions and peakVO₂ could not be confirmed. In professional handball players early repolarisation abnormalities were less frequent and LVmass was increased when compared with soccer players. The need for normal values for different types of sports is crucial to guarantee a proper evaluation of athletes.

https://www.thieme-connect.de/products/ejournals/pdf/10.1055/s-0032-1329549.pdf

Left ventricular mass and oxygen uptake in top handball athletes.

BACKGROUND AND OBJECTIVE Echocardiographic tissue Doppler imaging (TDI) has been proposed for differentiating between constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM). The aim of this retrospective study was to analyse TDI in patients with severe diastolic dysfunction associated with proven constrictive pericarditis or restrictive cardiomyopathy. PATIENTS AND METHODS The cohort included 34 consecutive patients (24 men. 10 women; mean age 58 12 years), 20 of whom had proven CP (pericardectomy) and 14 had RCM due to amyloidosis (proven by biopsy). Tissue Doppler Imaging was performed online by pulsed-wave TDI at the lateral and septal mitral annulus in the four-chamber view. Filling pressures were measured invasively. RESULTS 20 of the 34 patients (60%) were in NYHA class III. 19 of the 34 patients were in sinus rhythm (56 %) and 15 had atrial fibrillation. Left ventricular systolic function was normal in all patients with CP. Eight patients with RCM had normal, 3 patients near normal and 3 patients slightly impaired left ventricular contractile function (EF 50-55% and EF 40%, respectively). Respiratory variation of the transmitral inflow was increased in 10 of 12 patients with CP and sinus rhythm. TDI of the early diastolic velocity across the mitral annulus E} was significantly higher in patients with CP than in those with RCM at the septal and at the lateral mitral annulus (13.8 4.2 cm/s vs. 4.0 1.2 cm/s; p < 0.01 and 11.4 3.4 cm/s vs. 4.4 1.7 cm/s; p < 0.01, respectively). A cut-off value 8 cm/s for the diagnosis of RCM showed a sensitivity of 100% and a specificity of 90% (septal) and 80% (lateral), respectively. The E/E}ratio also was significantly different between both groups (septal: 11.2 8.8 vs. 25.1 8.7; p < 0.01). CONCLUSION TDI of the early diastolic velocity of the mitral annulus E} makes it possible to differentiate between constrictive pericarditis and restrictive cardiomyopathy and should be part of the echocardiographic work-up in clinical routine.

T. Kottmann

Papers

The occurrence of atrial fibrillation in former top-level handball players above the age of 50.

HELP apheresis in hypercholesterolemia and cardiovascular disease: efficacy and adverse events after 8,500 procedures.

Left ventricular mass and oxygen uptake in top handball athletes.

[Constrictive pericarditis or restrictive cardiomyopathy? Echocardiographic tissue Doppler analysis].

Konstriktive Perikarditis oder restriktive Kardiomyopathie