New-onset atrial fibrillation prediction: the HARMS2-AF risk score.

AIMS: Lifestyle risk factors are a modifiable target in atrial fibrillation (AF) management. The relative contribution of individual lifestyle risk factors to AF development has not been described. Development and validation of an AF lifestyle risk score to identify individuals at risk of AF in the general population are the aims of the study. METHODS AND RESULTS: The UK Biobank (UKB) and Framingham Heart Study (FHS) are large prospective cohorts with outcomes measured >10 years. Incident AF was based on International Classification of Diseases version 10 coding. Prior AF was excluded. Cox proportional hazards regression identified independent AF predictors, which were evaluated in a multivariable model. A weighted score was developed in the UKB and externally validated in the FHS. Kaplan-Meier estimates ascertained the risk of AF development. Among 314 280 UKB participants, AF incidence was 5.7%, with median time to AF 7.6 years (interquartile range 4.5-10.2). Hypertension, age, body mass index, male sex, sleep apnoea, smoking, and alcohol were predictive variables (all P < 0.001); physical inactivity [hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.96-1.05, P = 0.80] and diabetes (HR 1.03, 95% CI 0.97-1.09, P = 0·38) were not significant. The HARMS2-AF score had similar predictive performance [area under the curve (AUC) 0.782] to the unweighted model (AUC 0.802) in the UKB. External validation in the FHS (AF incidence 6.0% of 7171 participants) demonstrated an AUC of 0.757 (95% CI 0.735-0.779). A higher HARMS2-AF score (≥5 points) was associated with a heightened AF risk (score 5-9: HR 12.79; score 10-14: HR 38.70). The HARMS2-AF risk model outperformed the Framingham-AF (AUC 0.568) and ARIC (AUC 0.713) risk models (both P < 0.001) and was comparable to the CHARGE-AF risk score (AUC 0.754, P = 0.73). CONCLUSION: The HARMS2-AF score is a novel lifestyle risk score which may help identify individuals at risk of AF in the general community and assist population screening.

Role of plakophilin-2 expression on exercise-related progression of arrhythmogenic right ventricular cardiomyopathy: a translational study.

AIMS: Exercise increases arrhythmia risk and cardiomyopathy progression in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients, but the mechanisms remain unknown. We investigated transcriptomic changes caused by endurance training in mice deficient in plakophilin-2 (PKP2cKO), a desmosomal protein important for intercalated disc formation, commonly mutated in ARVC and controls. METHODS AND RESULTS: Exercise alone caused transcriptional downregulation of genes coding intercalated disk proteins. The changes converged with those in sedentary and in exercised PKP2cKO mice. PKP2 loss caused cardiac contractile deficit, decreased muscle mass and increased functional/transcriptomic signatures of apoptosis, despite increased fractional shortening and calcium transient amplitude in single myocytes. Exercise accelerated cardiac dysfunction, an effect dampened by pre-training animals prior to PKP2-KO. Consistent with PKP2-dependent muscle mass deficit, cardiac dimensions in human athletes carrying PKP2 mutations were reduced, compared to matched controls. CONCLUSIONS: We speculate that exercise challenges a cardiomyocyte "desmosomal reserve" which, if impaired genetically (e.g., PKP2 loss), accelerates progression of cardiomyopathy.

Acute glycaemic management before, during and after exercise for cardiac rehabilitation participants with diabetes mellitus: a joint statement of the British and Canadian Associations of Cardiovascular Prevention and Rehabilitation, the International Council for Cardiovascular Prevention and Rehabilitation and the British Association of Sport and Exercise Sciences.

Type 1 (T1) and type 2 (T2) diabetes mellitus (DM) are significant precursors and comorbidities to cardiovascular disease and prevalence of both types is still rising globally. Currently,~25% of participants (and rising) attending cardiac rehabilitation in Europe, North America and Australia have been reported to have DM (>90% have T2DM). While there is some debate over whether improving glycaemic control in those with heart disease can independently improve future cardiovascular health-related outcomes, for the individual patient whose blood glucose is well controlled, it can aid the exercise programme in being more efficacious. Good glycaemic management not only helps to mitigate the risk of acute glycaemic events during exercising, it also aids in achieving the requisite physiological and psycho-social aims of the exercise component of cardiac rehabilitation (CR). These benefits are strongly associated with effective behaviour change, including increased enjoyment, adherence and self-efficacy. It is known that CR participants with DM have lower uptake and adherence rates compared with those without DM. This expert statement provides CR practitioners with nine recommendations aimed to aid in the participant's improved blood glucose control before, during and after exercise so as to prevent the risk of glycaemic events that could mitigate their beneficial participation.

Brief recommendations for participation in leisure time or competitive sports in athletes-patients with coronary artery disease: Summary of a Position Statement from the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC).

This paper presents a brief summary of the recommendations from the Sports Cardiology section of the European Association of Preventive Cardiology (EAPC) on sports-participation in patients with coronary artery disease, coronary artery anomalies or spontaneous dissection of the coronary arteries, all entities being associated with myocardial ischaemia.1 Given the wealth of evidence supporting the benefits of exercise for primary and secondary prevention of coronary artery disease, individuals should be restricted from competitive sport only when a substantial risk of adverse event or disease progression is present. These recommendations aim to encourage regular physical activity including participation in sports and, with reasonable precaution, ensure a high level of safety for all individuals with coronary artery disease. The present document is based on available current evidence, but in most instances because of lack of evidence, also on clinical experience and expert opinion.

Early repolarization patterns associated with increased arrhythmic risk are common in young non-Caucasian Australian males and not influenced by athletic status.

BACKGROUND: Early repolarization (ER) with a horizontal ST segment (ST-h) and high-amplitude J waves in the inferior leads is associated with an increased risk of cardiac arrhythmic death. The effect of ethnicity and athletic status on this increased-risk ER pattern has not been established. Aboriginal Australian/Torres Strait Islander and Pacific Islander/Maori (non-Caucasian [non-C]) subjects are well represented in Australian sport; however, the patterns and prevalence of ER in these populations are unknown. OBJECTIVE: The purpose of this study was to assess the prevalence and effect of athletic activity on ER patterns in young non-C and Caucasian (C) subjects. METHODS: Twelve-lead ECGs of 726 male athletes (23.8% non-C) and 170 male controls (45.9% non-C) aged 16-40 years were analyzed for the presence of ER, defined as J-point elevation (J wave, QRS slur, or discrete ST elevation) ≥0.1 mV in ≥2 inferior (II, III, aVF) or lateral (I, aVL,V4-V6) leads. ST morphology was coded as horizontal (ST-h) or ascending (ST-a). "Increased-risk ER" was defined as inferior ER with ST-h and J waves >2 mV. RESULTS: Regardless of athletic status, ER and increased-risk ER were more prevalent in non-C than in C subjects (53.8% vs 32% and 7.6% vs 1.2%, respectively, P <.0001). Whereas lower heart rate, larger QRS voltage, and shorter QRS duration were predictors of ER, non-C ethnicity was the only independent predictor of increased-risk ER (odds ratio 17.621, 95% confidence interval 4.98-62.346, P < .0001). CONCLUSION: ER patterns associated with increased arrhythmic risk are more common in young non-C than C subjects and were not influenced by athletic status. The long-term clinical significance of ER in these populations is yet to be determined.

One- and two-dimensional estimation of right and left ventricular size and function-comparison with cardiac magnetic resonance imaging volumetric analysis.

BACKGROUND: Estimations of right ventricular (RV) and left ventricular (LV) size and function based on 1D and 2D measures are commonly used. However, their correlation with volumetric analysis methods is not well documented. METHODS: We analysed a series of subjects undergoing CMR (n=30). Contiguous short axis cine imaging was obtained to assess RV and LV volumes and function. Standard short and long axis cine imaging were performed to evaluate linear and planimetric dimensions as well as functional analysis. RESULTS: Linear and planimetric measurements of the RV in standard long and short axis views correlated weakly with standard volumetric measurements (r=0.34-0.73). RV ejection fraction (EF), when calculated from single plane functional analysis correlated only moderately with the volumetric EF (r=0.75, p<0.001). In contrast, estimation of LV volumes, mass and EF by biplane area-length method demonstrated excellent correlation with volumetric data (r=0.89, 0.92 and 0.91, p<0.001 for all). CONCLUSION: Two-dimensional estimations of volume and function correlate well with LV volumetric analysis, but not with RV volumetric analysis. Estimation of RV size and function based on linear or planimetric assumption models should be performed and interpreted with caution.

Three-dimensional cardiac rotational angiography: effective radiation dose and image quality implications.

AIMS: Three-dimensional rotational angiography (3DRA) is a promising new online tool for 3D imaging during cardiac ablation procedures. No precise data exist concerning its associated radiation dose. The current study evaluated the effective dose (ED) of cardiac rotational angiography and its relation to patient properties, imaging system input settings, and quality of reconstructed 3D images. METHODS AND RESULTS: We performed Monte Carlo simulation-based radiation dose calculations in 42 patients referred for ablation of cardiac arrhythmias. Detailed tube setting information from the 3DRA system (Siemens Axiom Artis dBC with Syngo DynaCT Cardiac software) was used to provide an accurate input for dose calculations in all 248 frames used during image acquisition. Our calculations yielded an overall mean ED of 6.6 +/- 1.8 mSv (based on ICRP 103 weighing factors). Manual collimation of the radiation beam can reduce ED by more than 20%. Image quality did not significantly relate to patient body mass index (BMI), dose per frame setting, or dose-area product (DAP), but was rather explained by contrast filling, cardiac motion reduction, and absence of image reconstruction artefacts. In the system evaluated, DAP values are nearly independent from BMI (R(2) = 0.30), due to its technical specifications. Therefore, patient BMI showed an unexpected strong inverse relation to ED. CONCLUSION: Three-dimensional rotational angiography can be performed with acceptable patient radiation dose, comparable to cardiac CT. With the 3DRA system studied (Siemens Axiom), slender patients may currently receive unnecessarily high radiation doses when compared with obese patients, so that further dose reduction seems feasible for many patients. Adequate collimation is imperative to limit patient exposure.

Apical ballooning syndrome during treatment with a vascular endothelial growth factor receptor antagonist.

Apical ballooning syndrome (ABS) describes acute regional myocardial dysfunction and has a strong association with emotional stress and female sex. Whilst catecholamine excess has been described in this condition, the precise etiology remains elusive. We report the atypical case of a 61 year old male who developed ABS in the absence of a clear precipitant. His concurrent treatment with a vascular endothelial growth factor (VEGF) receptor antagonist may provide an insight into the pathogenesis of this enigmatic condition. We present a biologically plausible explanation as to why VEGF antagonism may have an important role through its modulation of nitric oxide and catecholamine effects. This hypothesis may also provide an important insight into the cardiovascular toxicities associated with this class of drug. In addition, we report the success of treatment with a beta blocker in ABS complicated by a severe left ventricular outflow tract obstruction.