In this prospective pilot study, we aimed to evaluate the ability of cardiac magnetic resonance imaging (CMR) parameters of right ventricular function and pulmonary artery stiffness to identify pulmonary hypertension (PH), predict major adverse cardiovascular events (MACEs) in patients with secondary PH due to chronic obstructive pulmonary disease (COPD), and to estimate a prospective sample size necessary for a reliable power of the study. Thirty consecutive patients with COPD and suspected secondary PH were assessed by clinical examination, the six minute walk test, echocardiography, right heart catheterization and CMR, and followed–up for a mean period of 16 months to identify MACEs . Among CMR parameters of pulmonary artery stiffness, pulse wave velocity (PWV) yielded the best sensitivity (93.5%) and specificity (92.8%) for identifying PH, as diagnosed by cardiac catheterization. Moreover, PWV proved to be a valuable predictor of MACEs . In conclusion, PWV by phase-contrast CMR can accurately identify PH in patients with COPD and may help stratify prognosis. Risk factors such as advanced age and active smoking are often associated with inflammation2, involving neurohumoral and metabolic changes that contribute to the development of both COPD and heart failure3. The estimated prevalence of heart failure in COPD is >20%4, higher than in age-matched controls with similar cardiovascular risk profiles5. PH is a common occurrence in COPD patients, and is associated with poor exercise capacity and higher mortality rates, which are not exclusively justified by lung impairment itself 7. More severe COPD is associated with a higher incidence of PH8, occurring in >50% of the patients who are enlisted for lung transplantation9. Data regarding the real incidence of mild to moderate COPD, however, are scarce, as large epidemiological trials have not been performed. The pattern and velocity of blood flow in the pulmonary circulation are both altered in PH10, as a consequence of decreased vascular compliance and increased PA stiffness, leading to increased resistance and additional wall stress11. Increased PA stiffness is associated with elevated afterload, exerting stress on the RV which first adapts by hypertrophy, then dilates, resulting in right heart failure12. As PA stiffness develops, dilatation also occurs and PA compliance decreases. As shown by previous studies, PA dilatation is associated with poor outcome in patients with COPD, since a PA: ascending aorta (AA) ratio >1 was shown to independently predict future acute exacerbations, diminished exercise capacity, clinically significant PH and mortality15. Invasive hemodynamic assessment of PA wall stiffness by right heart catheterization (RHC) is currently the standard for diagnosis, prognosis assessment and follow-up after treatment in PH patients. In several studies, invasively measured pulmonary artery pressure (PAP) was shown to associate with increased mortality16. Non-invasive methods, such as echocardiography17 and, more recently, cardiac magnetic resonance imaging (CMR)19 were used for PH assessment in combination with invasive modalities, leading to promising results. However, echocardiography can only be used for assessing the probability of PH, and studies that would endorse the use of CMR alone are still scarce.Chronic obstructive pulmonary disease (COPD) has already been acknowledged as a triggering factor for right heart failure and pulmonary hypertension (PH), due to its impact on right ventricular (RV) function and morphology, and on pulmonary artery (PA) remodellingOn these considerations, we aimed to conduct a prospective study that allowed us to evaluate RV function and relationship between PA stiffness indices using CMR and adverse long-term outcome in patients with COPD and suspected secondary PH.nd Department of Internal Medicine in Cluj-Napoca between October 2011 and October 2016.We conducted a prospective pilot study in which we included 30 consecutive patients previously diagnosed with COPD and suspected of secondary PH (test group) who were hospitalized for acute respiratory failure in the 220; (2) confirmed diagnosis of acute exacerbation defined as aggravated dyspnoea, cough, or sputum production warranting a change in therapy; 3) high probability of PH by echocardiographic criteria (tricuspid regurgitation velocities >3.4 m/s); 4) absence of other factors that might have induced PH . Exclusion criteria were: 1) life expectancy of less than a year due to PH or other diseases; 2) contraindications for CMR ; 3) time interval between echocardiography, RHC and CMR > 10 days. Each enrolled patient was submitted to a standard investigation protocol which included history taking, physical examination, chest radiographs, pulmonary function tests and arterial blood gases, echocardiography, six minutes walk test, and Holter ECG monitoring for 24 hours. All tests were performed within 10 days after admission, provided that the patients had been stabilized by standard therapy with bronchodilators , short courses of oral or intravenous corticosteroids, n = 29; oxygen therapy, n = 8; antibiotics, n = 17; and diuretics, n = 11). The cardiovascular risk profile was established in each case, based on personal and family history, laboratory findings and known exposure to toxins . The investigators analysing CMRs were blinded to RHC results.Patients were included in the study provided they fulfilled the following criteria: (1) confirmed diagnosis of COPD, according to the criteria of the Global Initiative for Chronic Obstructive Lung DiseaseThe test group was compared against a control group of 30 healthy volunteers, matched for age and sex, who were submitted to a query excluding any history of chronic disease, any current symptoms or ongoing treatment for a chronic ailment, with normal clinical examination and normal electrocardiogram, chest radiographs, pulmonary function tests, echocardiography, Holter ECG monitoring for 24 hours and CMR. The healthy volunteers were enrolled within the same time span as test group patients.The study was approved by the Ethics Committee of the Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca and conducted in accordance with the Declaration of Helsinki. All patients and healthy volunteers signed an informed consent at enrolment.All data have been collected by and are the intellectual property of the authors.Clinical follow-up was accomplished by clinical evaluation during hospital visits, telephone house-calls, or both at six month intervals until October 2016. In order to analyse event-free survival, we recorded the first occurring event from the following: death or aborted death from cardiac cause, sustained ventricular tachyarrhythmia, or hospitalization for heart failure. Hospitalizations due to non-cardiac causes were not considered significant events.20.Pulmonary function was assessed using a water-sealed Collin Survey II volume displacement spirometer . Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured with the purpose of diagnosing and grading COPD. Persistent airflow limitation and COPD were diagnosed in the presence of a FEV1/FVC ratio of less than 0.70. COPD was graded as mild , moderate (50–79%), severe (30–49%), and very severe (<30%)21. Images were recorded and analysed off-line to accurately quantify left ventricular (LV) and RV systolic and diastolic function. LV ejection fraction was calculated based on Simpson’s modified single plane method from the apical 4-chamber view and considered normal if ≥55%. Systolic PAP was calculated as the sum between the RV-right atrium (RA) gradient, as measured on the tricuspid regurgitation flow, and the RA pressure; the latter was estimated by measuring the inferior vena cava diameter and collapse with a sniff. The probability of PH by echocardiography was considered high for tricuspid regurgitation velocities >3.4 m/sec21.All images were acquired on an Aloka ProSound 5500  echocardiograph with a wide-angle phased-array 2.5 MHz transducer. Measurements were performed according to previously published guidelines22.RHC was performed to measure RA pressure, systolic, diastolic and mean PAP, pulmonary capillary wedge pressure (PCWP), and cardiac index, assessed by the thermodilution method. The pulmonary vascular resistance (PVR) index was calculated as the difference between mean PAP and mean PCWP divided by the cardiac output index in Wood units. PH was considered present if mean PAP ≥ 25 mmHgCMR ECG-gated images were acquired during apnoea with a 1.5-Tesla magnet  using a dedicated surface coil for radio frequency signal detection. Patients were required to hyperventilate briefly, then exhale and hold their breaths during image acquisition.2; matrix 192 × 192 pixels; voxel size 1.9 × 1.9 × 6 mm; 25–40 ms temporal resolution reconstructed to 25 cardiac phases. Standard late gadolinium enhancement (LGE) images were acquired 10 minutes after the intravenous injection of a contrast agent  - 0.2 mmol/kg. Images were acquired in long and short axis views using a segmented inversion-recovery gradient-echo sequence after adjusting inversion time to optimize nulling of apparently normal myocardium. Brachial systolic and diastolic blood pressures were measured during the CMR SSFP acquisitions.Firstly, standard localized views and contiguous short-axis and 4-chamber cine views covering both ventricles from base to apex were obtained by standard steady-state free precession (SSFP) cine CMR sequences in order to evaluate ventricular volumes and function. Pre-contrast imaging parameters were recorded by a standard protocol: repetition time/echo time 3.6/1.8 ms; flip angle 60°; slice thickness 6 mm; field of view 360 × 360 mm23. To record PA stiffness parameters, the following specifications were applied to a free-breathing phase-contrast sequence: repetition time/echo time 7/5 ms; flip angle 15°; slice thickness 6 mm; field of view 360 × 360 mm2; matrix 256 × 256 pixels; voxel size 2.2 × 1.8 × 6 mm; <35 ms temporal resolution; 20 reconstructed cardiac phases; velocity encoding 150 cm/sec10. For the free-breathing sequences, the average of 2 measurements was usedPhase-contrast sequence acquisition at the level of the main PA was made using a SSFP sequence of the RV outflow tract following an orthogonal plane to optimally visualise the main PA and pulmonary valve, provided that the imaging plane remained between the pulmonary valve and the PA bifurcation for the entire duration of the cardiac cycleCine and phase contrast images were evaluated by two experienced observers (one cardiologist and one radiologist) blinded to all clinical data, using specialized software .Endocardial and epicardial borders were traced semi-automatically on short-axis cine images covering the entire LV and RV in order to measure end-diastolic and end-systolic LV and RV volumes, ejection fractions and end-diastolic LV mass. End-diastolic LV and RV mass to volume ratios were calculated and used to assess concentric remodelling. The maximum left atrium (LA) and RA areas were measured in all patients from the 4-chamber view. All volumes were indexed to body surface area. Tricuspid annular plane systolic excursion (TAPSE) was measured from the mid-four-chamber cardiac view to assess RV longitudinal motion. RV remodelling was defined as one or more of the following: the RV mass to RV end-diastolic volume ratio, the RV mass to RV end-systolic volume ratio and the RV/LV mass ratio. The presence/absence and location of LGE in both the LV and RV were also assessed and recorded.10:PA elasticity (%) – the variation in luminal area during the cardiac cycle: .PA distensibility (%/mmHg) – the variation in luminal area during the cardiac cycle for a given change in pressure: (PA elasticity/systolic PA pressure – diastolic PA pressure).2/mmHg) – absolute changes in luminal area for a given pressure variation: /(PA pulse pressure).PA compliance (mm3/mmHg) – the variation in volume  during the cardiac cycle for a given pressure variation: (RV stroke volume/(PA pulse pressure).PA capacitance  × minimal area/.Stiffness index beta: the ln (systolic PAP/diastolic PAP)/PA elasticity.et al.24: PWV = √∆Q2/∆A2; Q is the flow and A is the area through the PA. The contours for the main PA cross-section were manually traced on the magnitude images, with the purpose of determining the maximal and minimal PA areas, as well as peak and average velocities of the PA flow using specialized software (Syngo.Via VB20A). The program then automatically calculated flow and velocity data. Main PA and AA diameters were measured at the level of the PA bifurcation.Pulse wave velocity (PWV) was calculated as described by Davies PA stiffness assessment included the following parametersData was tested for normality by the The Kolmogorov-Smirnov test. Data with normal distribution were expressed as mean ± standard deviation (SD), data with non-normal distribution – as median value ± interquartile range (IQR), and relative frequencies for categorical variables were expressed in percentages. Variables with normal distribution were processed using the Student’s t test, while variables with non-parametric distribution were analysed by the ANOVA test. Baseline patient characteristics, echocardiography, CMR measures, and invasive hemodynamics were compared between patient groups using Fisher’s exact test or a Kruskal–Wallis rank sum test. Spearman’s coefficient was used to analyse correlations between RV function, PA stiffness and PAP. Pending the results of univariable analysis, multivariable analysis was performed to assess independent correlations between PAP, RV remodelling parameters and PA stiffness indices. The relationship between the six-minute walk test distance and PA stiffness was tested by linear regression analysis. Areas under the curves (AUC) were calculated by receiver-operator characteristic (ROC) curve analysis with the purpose of determining the sensitivity, specificity, positive predictive value and negative predictive value of PA stiffness parameters for diagnosing PH, with 95% confidence interval (CI). Results were graphically represented. Event-free survival (time to first event) was generated by the Kaplan–Meier method and survival curves were compared by the log-rank test. A Cox hazards model was used to test the association between the composite end-point for adverse outcomes  and baseline co-variables, with results presented as hazard rations (HRs) with 95% CI. The statistical analysis was performed with MedCalc for Windows, version 16.1.2 ; p values < 0.05 were considered statistically significant.In the test group, COPD was quantified as moderate in 11 patients, severe in 16 and very severe in 3 patients. Among all COPD patients included in the test group, 16 patients with PH were identified. Patients’ demographic data, laboratory findings, pulmonary function test parameters, echocardiography and RHC characteristics are summarized in Table During a mean follow-up period of 16 (6 to 38) months, 7 patients had majors cardiovascular events, as further described: cardiac death due to atrioventricular dissociation (n = 1); Holter ECG-documented ventricular tachyarrhythmia (n = 1), and hospitalization for heart failure (n = 5).CMR characteristics are detailed in Table Spearman’s coefficient analysis revealed significant associations between stiffness indices assessed by CMR, and PAP and PVR determined by RHC. Results are detailed in Table PA elastic modulus was strongly and directly correlated to mean PAP and systolic PAP, as was minimal PA area. The PA:AA diameter ratio was also strongly correlated to the PVR index, although associations to mean and systolic PAP were only moderate. The strongest associations emerged between PWV and mean and systolic PAP, with reasonably strong associations to the PVR index.PWV was negatively correlated to PA distensibility , compliance  and capacitance , and positively correlated to the elastic modulus  and stiffness index beta . The strongest associations occurred with PA capacitance and the elastic modulus.Positive correlations were obvious between the six-minute walk test distances and PA distensibility, compliance and capacitance. In addition to that, the six-minute walk test distance was negatively correlated to the PWV, elastic modulus and index beta after linear regression analysis Fig. .Figure 12 = 0.89, p < 0.001; and R2 = 0.89, p < 0.001, respectively). The predictive abilities of different PA stiffness indices for detecting PH as evaluated by ROC curve analysis have been compared (Fig. Multivariable analysis was used to explore the association between RV and PA morphological and functional parameters, as assessed by CMR, and mean and systolic PAP, in the presence of some potentially confounding factors, such as age or gender. To that purpose, four different models were constructed: model A included age, gender and RV mass index; model B – age, gender and PA elastic modulus; model C – age, gender and PWV; model D – age, gender, RV mass index, PA elastic modulus and PWV. Results are detailed in Table red Fig. .Table 4RFor assuring a 95% confidence, and 80% power of the study and based on the difference in MACE between groups, we have calculated a minimum required sample size of 40 patients in the test group for testing the ability of cardic MRI derived parameters to identify patients at risk for MACEs.23. Interestingly, in our study, PWV performed best among all PA stiffness parameters in identifying PH, as ROC curve analysis yielded reasonable performance indices.Currently, data regarding PWV measurements by CMR in patients with COPD are scarce. In our study, significant inverse correlations occurred between CMR-measured PWV and the indices for compliance and distensibility of the pulmonary vasculature, thus indicating that CMR could be used for early non-invasive identification of PH. As shown in previous studies, the assessment of PWV in major arteries provides crucial information regarding PA stiffness25. A previous CMR-based research on patients with COPD and no or mild hypoxemia revealed that RV mass was increased in test patients by comparison with healthy volunteers despite normal RV systolic function, suggesting that RV hypertrophy is the earliest sign of RV pressure overload, occurring as an adaptation process26. Another study comparing healthy volunteers to COPD patients with or without PH supported the same hypothesis; the study showed that changes suggesting RV hypertrophy were more obvious in COPD patients without PH vs. healthy controls, with little increase in patients with COPD and PH27. RV dilatation is also an essential component of RV remodelling. In our study, CMR measurements of RV dimensions, as well as RV end-diastolic volumes were significantly more elevated in COPD patients. Previous research has shown that larger RV volumes measured by CMR were an independent predictor of higher overall and cardiovascular mortality28.In addition to that, the results of our research highlighted the presence of right chamber remodelling assessed by echocardiography and CMR in patients with secondary PH due to COPD. Right chamber dimensions and RV mass were considerably elevated in test group patients by comparison with healthy volunteers, which was expected, considering the fact that the RV responds to elevated pulmonary pressures by progressive hypertrophy, followed by dilatationet al. who also showed improvement of this parameter after specific vasodilator treatment29, while van Wolferen et al. demonstrated that reduced RV stroke volume was an independent predictor of increased mortality and treatment failure30.Patients in our study were only admitted to the test group provided they had evidence of PH. In our research, CMR examination revealed impaired RV systolic function, as assessed by TAPSE, the RV ejection fraction and RV stroke volume in COPD patients by comparison with healthy volunteers. RV stroke volume reduction was also obvious in a previous study by Roeleveld et al., diminished TAPSE was shown to be highly predictive of increased mortality in patients with COPD and PH31; similar results were obtained by Forfia et al. who demonstrated significant correlations between TAPSE and right chamber remodelling, as well as other indices of impaired RV systolic function, and showed that patients with PH and decreased TAPSE had lower survival32.In a study by Kjaergaard 33. Interestingly, there was barely any correlation to RV end-diastolic volumes, an observation which also emerged from the study of Stevens et al.19. These results may suggest that RV dilatation with no impairment in RV systolic function is less likely to be accompanied by significantly increased PA stiffness. In fact, RV systolic impairment may be a consequence of pressure overload triggered by persistent severely increased PA stiffness, since a previous study showed that PA stiffness indices became impaired before significant increases in resting systolic PAP10, and may, therefore, have a significant contribution to disease progression. Accordingly, we intended to establish correlations between systolic PAP and PA stiffness indices; the strongest linear correlations were obvious between systolic PAP and PA distensibility, compliance, capacitance and elastic modulus, which is consistent with the results of previous studies in which either CMR10 or intravascular ultrasound were used for determining pulmonary stiffness35.Our CMR-based examinations also showed significant differences in PA stiffness indices between test group patients and healthy volunteers. In addition to that, statistical analysis revealed important correlations between PA stiffness indices, such as PA elasticity, distensibility, capacitance, compliance, elastic modulus, stiffness indices alpha and beta, and RV remodelling and function parameters, such as RV ejection fraction, RV mass indexed, RV stroke volume indexed, TAPSE, and RV end-systolic volume; these findings are consistent with results from other studiesInterestingly, low PWV values at CMR were shown to predict survival, a novel discovery, undocumented, to our knowledge in previous research. However, results should be interpreted with caution, considering the low number of patients, and implicitly the low number of individuals who experienced MACEs.Indeed, the main limitations of the current study are related to the rather small number of participants. We aimed to diminish the impact of this limitation on our results by carefully selecting the study population using well established criteria and following a standard detailed examination protocol. Also, the study needs to be continued until the minimal estimated sample size is reached.36 rendered this examination superfluous. Further research on a larger number of patients may help consolidate the results of the current study.CMR examinations were carefully performed, yielding good quality images. 2D-velocity-encoded CMR allowed accurate non-invasive measurements of aortic blood flow parameters with good temporal and spatial resolutions. Although 4D phase-contrast CMR was not available for the assessment of the patients in this study, the limited temporal and spatial resolutions that have been reported for such techniquesCMR phase-contrast imaging may provide an extensive and accurate assessment of right chambers remodelling and PA stiffness in patients with COPD. In the future, it may become a valuable non-invasive tool for quantifying PH, provided that its value is further confirmed by more extensive studies. PA stiffness assessment by CMR seems to be promising in terms of early identification of pulmonary vascular disease, which may result in earlier diagnosis and treatment onset, thus diminishing arterial remodeling progression. Moreover, CMR-derived PA stiffness indices, particularly PWV, may be useful for predicting MACEs. However, our research is only hypothesis generating and larger studies are necessary to confirm these findings.


Smoking is known to increase cardiovascular events, but the association and mechanisms between smoking and ventricular arrhythmic events in dilated cardiomyopathy (DCMP) are unknown. The purpose of this study is to investigate the hypothesis that smoking is associated with sudden cardiac death (SCD) and ventricular arrhythmia in DCMP patients. We enrolled 378 patients who underwent cardiovascular magnetic resonance imaging (cMRI) and were diagnosed with DCMP at two general hospitals in Korea. The clinical data and left ventricular late-gadolinium enhancement (LV-LGE) of all patients were analyzed according to being never-smokers or smokers. Smokers were more likely to be male than never-smokers, but there was no other clinical difference between them. Smokers had a greater LV-LGE ratio, and multi-segment involvement of LV-LGEs. Smoking and a low left ventricular (LV) ejection fraction were significant predictors of the presence of LV-LGEs even after adjusting for optimal medical therapy. In addition, smokers had a higher fatal ventricular arrhythmic  and FVA + SCD, and ex-smokers had a similar FVA to never-smokers during 44.3 ± 36.4 months of follow-up. Finally, smoking independently increased the FVA + SCD even after adjusting for the clinical variables and LV-LGE. Smoking is associated with a multi-segmental involvement of LV-LGE and increased FVA + SCD in DCMP patients when compared to never-smokers. In the U.S., approximately 140,000 premature deaths per year from cardiovascular disease are triggered by cigarette smoking2. Although the exact components and mechanism of cigarette smoking that are related to increased cardiovascular morbidity are unclear, cigarette smoking is known to increase inflammation, thrombosis, oxidation of low-density lipoprotein cholesterol, and trigger fibrotic processes in body tissues including atrial muscle6. Cardiac fibrosis has a strong correlation with systolic dysfunction, diastolic dysfunction, and abnormal electrical excitation; thus, it is also known to increase the incidence of arrhythmias, ventricular tachycardia, and sudden cardiac attacks. Studies reveal that the extracellular matrix in between cardiac myocytes slows the electrical conduction and the myofibroblasts produce ectopic electrical activity, which all-together eventually form micro-reentrant circuits within the endocardial tissue, leading to arrhythmogenesis3. Therefore, cardiac fibrosis is suggested as a fundamental factor for predicting the cardiovascular morbidity and mortality by modifying the mechanical, electrical, and vasomotor function7. In the clinical field, cardiac fibrosis can be evaluated through late-gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) imaging8. Recent studies have shown an excellent agreement of the histologic pattern of cardiac fibrosis with in vivo CMR imaging. Using LGE-CMR imaging, the results exposed that the likelihood of the developing arrhythmias in dilated cardiomyopathy (DCMP) is higher in people with midwall fibrosis than in those without fibrosis. Moreover, it has been reported that myocardial fibrosis assessed by LGE-cMRI is associated with cardiovascular mortality and sudden cardiac death (SCD) in patients with dilated cardiomyopathy (DCMP)9. In fact, it is known that as fibrosis measured by the LGE-CMR increases by 3%, the all-cause mortality increases by a mean of 55%7. Therefore, the aim of this study was to investigate the association between smoking and myocardial fibrosis assessed by LGE-CMR in DCMP patients and to determine whether the smoking is associated with incidence of arrhythmic events due to myocardial fibrosis including ventricular arrhythmias and sudden cardiac death (SCD). We limited our case-group to non-ischemic cardiomyopathy (NICM) patients to exclude ventricular fibrosis associated with coronary artery disease10. Further, to support our hypothesis, we divided our group into smokers and never-smokers. Then we compared the amount of cardiac fibrosis within the two groups and analyzed the relationship between left ventricular fibrosis using the LGE by CMR imaging and the incidence of arrhythmic events including ventricular arrhythmias, and SCD.Cigarette Smoking is a well-known risk factor for significantly increasing the cardiovascular morbidity and mortality11. Thus, studies that were included in this analysis met the following criteria. (1) Patients with a left ventricular ejection fraction (LVEF) of <50% without regional wall-motion abnormalities, (2) LV diastolic dimension of >55 mm, (3) symptoms or signs of heart failure according to the Framingham criteria, and (4) the absence of significant coronary artery disease (CAD) on angiography or 3-dimensional cardiac CT (to ensure exclusion of >50% obstructions of one or more coronary arteries) were included in this study12. Patients with significant valvular heart disease of more than moderate to severe, hypertrophic cardiomyopathy, restrictive cardiomyopathy, prior cardiac surgery, or structural heart disease were excluded.The study protocol was approved by the institutional review boards of two general hospitals. The study protocol was approved by the Institutional Review Board of Yonsei University Health System and Ewha Womans University Mokdong Hospital and conducted in accordance with the tenets of the Declaration of Helsinki (EUMC 2015-07-046-016). All patients provided written informed consent. A total of 378 patients who were diagnosed with non-ischemic DCMP and underwent CMR imaging between May 2003 and December 2015 at two tertiary hospitals in Korea were retrospectively enrolled in this study. All patients underwent a detailed history and clinical evaluation including a 12-lead electrocardiogram (ECG), 2-dimensional transthoracic echocardiography, contrast enhanced CMR, and coronary angiography or coronary computed tomography (CT). DCMP was defined in accordance with the World Health Organization/International Society and Federation of Cardiology’s guidelines14.All patients underwent trans-thoracic echocardiography . The LVEF, chamber size , transmitral flow velocity , and tissue Doppler images of the mitral annular septal area  were acquired according to the American Society of Echocardiography guidelinesThe information on the exposure of smoking and alcohol was acquired from patient questionnaires or medical records at the first visit to the hospital. (1) smokers were defined as having a smoking exposure if they used more than 100 cigarettes in their lifetime (ex-smoker + current smokers), (2) never-smokers were defined as those with a smoking exposure of less than 100 cigarettes over their lifetime, (3) ex-smokers were defined as those with smoking cessation from at least 1 year prior, and (4) current smokers were defined as those with a smoking exposure of more than 100 cigarettes, and that had smoked within the last year. The definition of alcohol intake was described as a frequency of ≥1–3 times per month. The medication history of the patients was analyzed based on the chart review of their use of the following drugs. Angiotensin converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs), beta-blockers (BBs), diuretics, aldosterone antagonists, statins, digoxin, and amiodarone were included, and the use of each medication was defined for a prescription of more than at least 3 months regardless of the dose.15.All CMR imaging studies were performed using a 1.5-T scanner  with a phased array cardiac coil. electrocardiogram (ECG)-gated cine imaging was performed using a balanced steady-state free precession sequence with the following parameters: TR/TE, 3.4/1.7 ms; flip angle, 50°; field of view, 360 × 360 mm; matrix, 256 × 256; slice thickness, 8 mm; 25 phases per cardiac cycle; average number of signals, 1; and short axis planes encompassing the entire LV without a slice gap. Delayed enhancement imaging was performed 10 minutes after an intravenous injection of gadolinium  at 2 mL/sec. Image acquisition was synchronized with the ECG in the mid-diastolic phase in order to minimize motion artifact. An inversion time (TI) was individually optimized to nullify the signal of the normal myocardium using a dedicated TI-determining sequence16, and each segment model was rearranged to the anterior, interventricular septum, inferior, and lateral wall. In addition, the junction between the LV and right ventricle (RV) was described as a focal, hyperintensity area confined to the junction of the RV wall to the anterior and/or posterior interventricular septum, and multi-segment involvement was defined as involvement of more than 3 segments. An LGE quantification was performed. A semiautomatic segmentation of the endocardial and epicardial borders was performed in each short axis image in order to obtain the myocardial volume. The LGE volume was quantified using a full width at half maximum (FWHM) technique and the region of interest was drawn in the area of the maximum signal intensity of a visible LGE for the FWHM threshold. The myocardial and LGE volumes were determined as the sum of each area for each slice, multiplied by the slice thickness. The percentage of the LGE was calculated by dividing the LGE volume by the myocardial volume, with a quotient multiplied by 100. We used the median value as the cut-off of the LGE volume in the DCMP patients, and in this study, the median value of the LGE volume was 3.5%. We analyzed the patients after dividing the groups into those with an LGE extent of ≥3.5% and those with an LGE extent <3.5%. The CMR imaging was evaluated by three radiologists in each hospital for the location, and quantification of the LGE. As previously reported17, the inter-observer agreement between the first two readers was substantial . The intra-observer variability of the LGE quantification for the CV and ICC were 12.5% and 0.99 , respectively17.All CMR images were transferred to a dedicated software program for analysis . The images were reviewed by three radiologists  in consensus. Cine images were analyzed to determine the ventricular volume and ejection fraction using a semi-automatic segmentation in the software. The LGE was assessed using a modified 16-segment model of the LVAfter the standardized data collection was completed, all case records were reviewed for the purposes of obtaining additional information. Follow-up data were obtained by a detailed review of all medical records of all patients. Patients had regular follow-ups with or without a standard 12-lead ECG in the outpatient clinic every 3 to 6 months, or when symptoms occurred. Patients with symptoms suggestive of arrhythmias underwent ambulatory Holter monitoring (24 hours) and/or event recording. Patients without any symptoms were evaluated every year with 24-hour Holter monitoring. The analysis of the ECG Holter recordings focused on ventricular tachycardia (VT), either non-sustained (NSVT) or sustained (SuVT). NSVT was defined as a tachycardia (≥100 beats/min) of a ventricular origin that self-terminated within 30 seconds, and SuVT was defined as that which lasted for more than 30 seconds. Ventricular fibrillation (VF) that was identified by the QRS complexes had a markedly different morphology, axis, and amplitude and no obvious P waves were observed and the rate was irregular and usually greater than 300 beats per minute.18. In addition, the cause and date of death were confirmed by information from the National Population Registry of the Korea National Statistical Office, together with a review of all available clinical records at the time of death17.Implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy devices with a defibrillator (CRT-D) that were implanted for primary prevention were decided by the physician’s discretion and patient’s willingness. A routine ICD or interrogation  and ECG recordings at the time of the symptoms were used to document the occurrence of spontaneous VT during the follow-up period in all patients. An appropriate ICD intervention was defined as a device shock or anti-tachycardia overdrive pacing delivered in response to a VT and documented in the stored intracardiac ECG data. All interrogations were identified and adjudicated by two electrophysiologists (D.G.S. and J.B.P); who were blinded to the clinical data, including the CMR analyses. The outcomes of this study were defined as: (1) major ventricular arrhythmias (MVAs) including NSVT, SuVT, and VF and (2) fatal ventricular arrhythmias (FVAs), including SuVT and VF. We described SCD as an unexpected natural death from a cardiac cause within 1 hour from the onset of symptoms, in a person without any prior condition that would appear fatalContinuous variables are reported as the mean ± standard deviation (SD). Continuous variables were analyzed using independent t-tests. Normality was determined using the Kolmogorov-Smirnov goodness-of-fit test. Categorical variables were reported as numbers and percentages and were analyzed using Pearson’s chi-squared tests or Fisher’s exact tests, as appropriate. Cox regression and Kaplan-Meier analysis were performed for predictors of FVA(+SCD) and smoking or never smoking groups, respectively. A P-value ≤ 0.05 was considered statistically significant.A total of 378 patients  were enrolled for the analysis. Among them, there were 131 (34.7%) smokers, including 48 (12.7%) ex-smokers and 83 (22.0%) current smokers, and there were 247 (65.3%) never-smokers. Smokers more usually were male  and drank more alcohol  than never-smokers. However, there was no significant difference in the age and co-morbidities such as hypertension and diabetes , but, the age, gender, and LV dilatation did not have a significant association with the formation of an LV-LGE in the multivariate analysis Table . EspeciaIn an analysis of ventricular arrhythmias, the incidence of NSVTs did not exhibit any significant difference between never-smokers and smokers, but SuVTs  and VF  were significantly increased in smokers as compared to never-smokers Fig. . When coDuring a follow-up duration of 44.3 ± 36.4 months, smokers had significantly increased FVA events as compared to never-smokers  In patients with DCMP, smokers were more likely to be male, and have multi-segmental involvement, (2) smoking and alcohol intake were associated with the presence of an LV-LGE, regardless of the optimal use of HF medications and a geometric change in the LV, (3) smokers had an increased number of FVAs as compared to the never-smokers, and stopping smoking within more than 1 year may have a protective effect on FVAs, and (4) smoking was an independent predictor of FVAs or FVA + SCD in patients with DCMP.8. The reason is that the extent of the myocardial fibrosis can be determined by the LGE19, the presence of which predicts cardiac events occurring in patients with DCMP8. In various cardiovascular diseases, the detection of fibrosis is a useful assessment of myocardial viability20, and the presence of fibrosis is a better marker of VT inducibility than the LVEF21. The available evidence also has proven that myocardial fibrosis, demonstrated by LGE-CMR, is an important predictor of cardiac mortality in non-ischemic cardiomyopathy22. Therefore, it has been reported that the LGE-CMR might be a useful tool for selecting suitable patients for primary ICD implantations in patients with non- ischemic cardiomyopathy23. In the present study, an increased LV-LGE was associated with a low LVEF in patients with DCMP. This is in agreement with the findings from the previous studies8. We also found that an LV-LGE in DCMP patients was associated with a worse prognosis such as SCD and FVA events. These results are based on the theories of the previous studies and suggest that an evaluation of LV-LGEs in patients with DCMP is clinically important.The LGE-CMR has been routinely used for the assessment of myocardial fibrosis in patients with DCMP25. Additionally, the association between smoking and cardiomyopathy has also been proposed by several animal studies27. Possible mechanisms underlying the association between smoking and non-ischemic cardiomyopathy include cardiac muscle damage by a disturbance in the oxidative processes and cardiac susceptibility after viral infections28. Although it is well known that smoking increases the cardiovascular mortality and morbidity, the association between smoking and an LV-LGE in patients with DCMP is not yet clear. In this study, we found that the smoking was associated with the presence of an LV-LGE, and smokers had a greater ratio of LV-LGEs than never-smokers. Especially, alcohol and smoking were associated with the presence of an LV-LGE, even after adjusting for the use of optimal heart failure medications. Additionally, in our data, the incidence of SuVTs and VF was significantly increased in smokers as compared to never-smokers. These findings suggest that smoking might be related to an increase in an LV-LGE formation and the incidence of FVAs in patients with DCMP.It has been reported that smoking is associated with poorer outcomes in patients with DCMP29. The mechanism of myocardial fibrosis due to hypertension has been reported to be caused by left ventricular diastolic dysfunction31. In addition, several cellular mechanisms of diabetic myocardial fibrosis have been reported to include an impaired excitation-contraction coupling, reduced coronary flow reserve, inefficient energy production, and fibrotic remodeling32. In previous reports, hypertension and diabetes influenced the formation of more myocardial fibrosis, so that, thus causing ventricular arrhythmias34. However, in our data  was excluded. However, if NICM patients continuously smoke, it was not possible to exclude that ischemic events occurred during follow-up. Second, this study was a retrospective analysis, and included a select group of patients referred for treatment of cardiomyopathy. The data used in the study were acquired through a retrospective review of the patient’s charts. Thus, there was selection bias and limitations on the data acquisition. Third, only a few patients among those who met the indication for primary prevention received an ICD or CRT-D implantation. Therefore, fewer arrhythmic events in the patients might have been recorded due to suboptimal detection methods. Fourth, the patients did not undergo cardiac biopsy for the evaluation of the definite etiology and myocardial fibrosis. However, we excluded patients with features suggesting cardiomyopathies other than DCMP on CE-CMR. Fifth, diabetes and hypertension can affect myocardial fibrosis formation as well as smoking and can cause arrhythmias. However, there are limitations in comparing the single effects of smoking and alcohol consumption, diabetes, and hypertension, respectively. Especially, cardiomyopathic patients intaking alcohol are addicted to smoking, and patients with hypertension may have diabetes together. Therefore, it is difficult to prove the individual effect of each on myocardial fibrosis.This study had several limitations. First, NICM patients were classified by coronary angiography (CAG) and 3-dimensional cardiac CT assessment. At least in the early-stage of DCMP patientsOur study is the first to show a relationship between smoking and the formation of an LV-LGE in patients with DCMP. Smokers had a greater ratio of the LV-LGEs than never-smokers. Especially, alcohol and smoking were associated with the presence of an LV-LGE, even after adjusting for the use of optimal heart failure medications. Moreover, smokers had increased FVAs as compared to never-smokers. Importantly, the FVA free survival of ex-smokers was located between never- and current smokers, which represented that stopping smoking may have protective effects on FVAs. Therefore, a combined analysis of LV-LGEs and smoking is very important in DCMP patients and may be a useful marker for selecting patients with a high risk of FVAs and SCD.Supplementary Information


Early effective identification of high-risk patients for acute pulmonary embolism (APE) contributes to timely treatment. The pulmonary artery obstruction index (PAOI) in computed tomography angiography (CTA) is a semi-quantitative observation index, commonly used to evaluate the severity of a patient’s condition. This study explores the ability of PAOI to assess the risk stratification of APE. Thirty patients with APE were analysed. They were classified according to the guidelines, and the PAOI and cardiovascular parameters were measured in CTA. The difference of PAOI between different risk stratification patients was compared, and the predictive value of the PAOI for high-risk stratification was evaluated by the receiver operating characteristic curve. The correlation between PAOI and cardiovascular parameters was also analysed by Spearman correlation analysis. The PAOI in low- and high-risk patients was (33.2 ± 18.6)% and (68.1 ± 11.8)% respectively, and the difference was statistically significant. The PAOI was strongly predictive for high-risk patients. The cut-off value was 52.5%, with a sensitivity of 100% and specificity of 81.0%. The PAOI was correlated with the main cardiovascular parameters. We conclude that the PAOI in CTA is helpful for assessing risk stratification in patients with APE, which contributes to the selection of both the treatment plan and prognostic evaluation. It has been reported that APE may cause many complications such as cardiogenic shock, sudden death, etc5. The mortality rate can be as high as 31–36% for such cases6. If early diagnosis and effective anticoagulant therapy can be taken in time, the mortality rate can be reduced to 2–10%7. However, due to the lack of specific clinical symptoms and signs, pulmonary embolism is easily misdiagnosed or missed, and the best opportunity for treatment may therefore be missed9.Acute pulmonary embolism (APE) is a group of clinical and pathophysiological syndromes caused by embolism of an endogenous embolus  or an exogenous embolus (such as gas embolus) in the pulmonary artery or its branches10. In 2008, the European Society of Cardiology (ESC) suggested that the area of the embolism should be replaced with risk stratification11. In 2014, the ESC updated the “Guidelines on the diagnosis and management of acute pulmonary embolism”12. The guidelines described that the risk stratification during diagnosis should be combined with consideration of right heart function and myocardial injury. A reliable risk stratification is the cornerstone of APE treatment14, However, the method for risk stratification involves numerous clinical indicators, and is still restricted with regard to its clinical application.An accurate understanding of the developmental process of pulmonary embolism, as well as accurate risk stratification for the patient’s condition, can assist in making an appropriate treatment plan; thereby improving the curative effect for the patient16. In addition to the diagnosis and differential diagnosis, CTPA was also used to evaluate prognosis and so on. Based on CTPA, Qanadli et al. established a semi-quantitative analysis method for APE, called the pulmonary artery obstruction index (PAOI)17. It is reported that the PAOI was related to the severity of APE18. However, very little of the literature has focused on the correlation between PAOI and the risk stratification of APE. Therefore, the aim of this study is to determine whether PAOI can be used as a simple quantitative index to assess the risk stratification of APE.With the application of multi-slice spiral CT pulmonary angiography (CTPA), the accuracy of early diagnosis of APE is greatly improvedThe identification of the branches of pulmonary artery were showed in Fig. Direct signs: In combination with MPR, MIP and VR, the number and the location of the embolus were recorded. According to the position of embolus in the vessel lumen and the relationship between embolus and vessel wall, the emboluses were divided into three types: (1) The complete occlusion type was found in 42 vessels. MPR and MIP showed different filling defects in the lumen of arteries Fig. . VR showIndirect signs Fig. : There wt = 6.22, P < 0.01).There were 21 cases of low-risk patients and 9 cases of high-risk patients. The PAOI in low- and high-risk patients was (33.2 ± 18.6)% and (68.1 ± 11.8)%, respectively Fig. , and theP < 0.01), the negative predictive value was 69.2%, and the positive predictive value was 100%.The ROC curve of PAOI prediction for high-risk patients was shown in Fig. The cardiovascular parameters in low- and high-risk patients were shown in Table P < 0.05), LVd was negatively correlated with PAOI. The correlation with cardiovascular parameters was shown in Table The cardiovascular parameters MPAd, rPA, RVd and RVd/LVd were positively correlated with PAOI, and the correlation between RVd/ LVd and PAOI was the highest , thin-layer scanning and thin-layer reconstruction now possess greatly improved image resolution, powerful post-processing function and have the ability to collect large quantities of informationn = 20) and the hemodynamic stability group (n = 33) according to their hemodynamic status. There were significant differences in the PAOI. of two groups. ROC analysis revealed that the threshold value of PAOI for diagnosing hemodynamic instability was 48% (sensitivity 95% and specificity 76%)33. In 2010, some of the 73 patients with APE were divided into critical and non-critical restructures according to the clinical indicators. It was found that the PAOI was significantly higher than the non-critical recombination (median 43% vs 20%), and was related to the right cardiac insufficiency34. In 2012, researchers found that in the death and survival groups of patients with acute pulmonary embolism, an increase in PAOI was a risk factor for death in patients with acute pulmonary embolism. The negative predictive value of death reached 100% when the PAOI was less than 40%35.In 2009, 85 patients with suspected APE were examined by CTPA, of whom 53 were diagnosed with PE. The patients were divided into the hemodynamic instability group  predicts the patients with high risk, for which the sensitivity and specificity was 100% and 81.0%, respectively. Therefore, for APE patients, the higher the PAOI value, the higher the risk stratification is. As the risk stratification is closely related to the early mortality of patients, the measurement of PAOI has important reference value for clinical assessment of APE patients.This study further observed the correlation between PAOI and other cardiovascular parameters. The results showed that there was a correlation between PAOI and cardiovascular parameters. The correlation between PAOI and RVd/LVd was the highest, which was consistent with the previous study, suggesting that PAOI could prodict the severity of hemodynamic changes in APE patients. After the occurrence of APE, the embolus can cause pulmonary artery contraction through mechanical obstruction and nerve body fluid regulation and hypoxia, which leads to increased pulmonary circulation resistance and increased pulmonary arterial pressure in different degrees. The right ventricular and pulmonary vascular post load increases significantly when the patients are in a seriously compromised cardiovascular state, causing right ventricular and pulmonary vascular decompensation adjustment, even in the right ventricular and pulmonary vessels, and secondary acute right heart failure. Decompensation regulation mainly manifested as the dilatation of the right ventricle, the widening of the main trunk of the pulmonary artery, the localized dilatation of the upstream vessels of the embolic part and the compensatory expansion of the un-embolized pulmonary vessels. The main manifestations were a decrease of blood pressure and an increased likelihood of shock. The results of this study show that there were different levels of correlation between PAOI and cardiovascular parameters in APE patients. With the increase of PAOI, the pulmonary artery pressure increased and the cardiovascular parameters changed to varying degrees. The right ventricular function was most obvious. This maybe the reason why PAOI can predict high-risk patients.Although DSA pulmonary angiography is the gold standard for the diagnosis of pulmonary embolism, CTPA is the first choice for acute pulmonary embolism in emergency patients. CTPA has the advantages of being non-traumatic, capable of rapid imaging, high accuracy, and the production of a clear image. The distribution range and size can be used for three-dimensional imaging. Sem-quantitative analysis of PAOI is helpful for risk stratification in patients with acute pulmonary embolism, and it can be used to guide the treatment of patients. A limitation of this investigation is the small number of cases that were available to be included in the study. In the future, we will consider the application of PAOI in guiding the treatment of patients.The subjects of this study were the patients with APE admitted to the First Affiliated Hospital of Bengbu Medical College. Inclusion criteria were as follows: (1) there was visible arterial embolization in a CT image, (2) time of onset within 14 days, and (3) no thrombolytic or anticoagulant therapy was carried out before admission.Exclusion criteria were as follows: (1) chronic pulmonary hypertension or right ventricular wall thickening etc., (2) congenital heart disease, (3) coronary heart disease, (4) abnormal left heart function, (5) pulmonary and mediastinal diseases that may affect the diameter of pulmonary artery, and (6) poor image quality, such that the reconstruction could not be completed. A total of 30 cases were selected, including 14 males and 16 females, aged (64.9 ± 15.9) years.The study was approved by the Ethics Committee of The First Affiliated Hospital of Bengbu Medical College. All the participants provided their written informed consent to participate in this study.All methods were performed in accordance with the relevant guidelines and regulations.A General Electric (GE) Lightspeed 64-row spiral CT was used. The scanning range was selected from the thoracic inlet to the costophrenic angle in the supine position. The voltage and current of scanning parameters are 100 kV and 50 mA respectively. The layer thickness was set to 0.625 mm. A double cylinder high-pressure syringe was used for intravenous injection. The injection dose of Ioversol (I) (370 mgI/ml) was calculated according to the weight of 1 ml/kg, while the injection speed was maintained at rate of 4–5 ml/s and a double flow rate was maintained throughout. The scan started after the contrast agent was injected for 18–28 s. The original data were analysed by three-dimensional post-processing techniques such as multi-planner reformation (MPR), maximum intensity projection (MIP), and volume rendering (VR), to obtain the corresponding embolic locations, numbers, and morphological features. All the CT images were reviewed by two radiologists, independently. If there was any inconsistency between them, another board-certified radiologist participated in discussion until the results agreed with each other.The calculation formula for PAOI was as follows:n” represents the embolus score for a special pulmonary segment. Each lung is divided into 10 pulmonary segments, and each segment had a main pulmonary segmental artery. The names of all arteries are shown in Fig. In the formula, the “n” was from a minimum of 1  to a maximum of 20 .Three computational method were used Fig. . Firstlyd” represents the degree of thrombus for each artery, with a partial obstruction of 1 and a complete occlusion of 2  was measured. The diameter of ascending aorta (AAd) was measured at the same plane. The ratio of the diameter of pulmonary trunk to the diameter of aorta (rPA) was then calculated, and the calculation formula was as follows:Measurement of the maximum diameter of the short axis of left ventricle and right ventricle was as follows: On the horizontal axis image in CTA, the measuring line was drawn at the widest area of left ventricle and right ventricle. The maximum distances between the ventricular septum and the free wall of left and right ventricular were measured, which was defined as the diameter of left ventricle (LVd) and the diameter of right ventricle (RVd). The ratio of the RVd to LVd was then calculated (rRL), and the calculation formula is as follows:The risk stratification was performed with reference to ESC 2008 APE guidelines. (1) Shock or hypotension refers to the systolic pressure of the body circulation <90 mmHg or a decrease of the base value over 40 mmHg that lasts for more than 15 minutes. Those patients whose hypotension was caused by new arrhythmia, low blood volume, or infection were excluded. (2) Right ventricular dysfunction (RVD) refers to the observation of at least one of the following criteria: cardiac colour Doppler ultrasound indicated right ventricular systolic dysfunction, CT showed right ventricular enlargement, brain natriuretic peptide (BNP) elevation (>90 ng/L), NT-BNP increase (>500 ng/L), electrocardiogram (ECG) showed new onset complete or incomplete right bundle branch block, and ST segment elevation or depression or T wave inversion. (3) Myocardial injury: cardiac troponin I > 0.4 µg/L or troponin T > 0.1 µg/L.Patients with no right ventricular dysfunction and myocardial injury markers were classified as low-risk group, while patients with shock or persistent hypotension were classified as high-risk group.2 test was used for the qualitative data. The correlation between PAOI and cardiovascular parameters was analysed using Spearman correlation analysis. The maximum likelihood method for PAOI was used to fit the receiver operating characteristic curve (ROC) to the low-risk group and high-risk group, and the area under the curve (AUC) was calculated. P < 0.05 was considered statistically significant.Statistical processing was performed by using the SPSS 21 software package. Measured data in accordance with the normal distribution were expressed as mean ± standard deviation. Independent quantitative t-tests were used to compare the quantitative data between the groups, and a χ


Despite growing prevalence of online shopping, its impacts on mobility are poorly understood. This partially results from the lack of sufficiently detailed data. In this paper we address this gap using consumer panel data, a new dataset for this context. We analyse one year long longitudinal grocery shopping purchase data from London shoppers to investigate the effects of online shopping on overall shopping activity patterns and personal trips. We characterise the temporal structure of shopping demand by means of the duration between shopping episodes using hazard-based duration models. These models have been used to study inter-shopping spells for traditional shopping in the literature, however effects of online shopping were not considered. Here, we differentiate between shopping events and shopping trips. The former refers to all types of shopping activity including both online and in-store, while the latter is restricted to physical shopping trips. Separate models were estimated for each and results suggest potential substitution effects between online and in-store in the context of grocery shopping. We find that having shopped online since the last shopping trip significantly reduces the likelihood of a physical shopping trip. We do not observe the same effect for inter-event durations. Hence, shopping online does not have a significant effect on overall shopping activity frequency, yet affects shopping trip rates. This is a key finding and suggests potential substitution between online shopping and physical trips to the store. Additional insights on which factors, including basket size and demographics, affect inter-shopping durations are also drawn. Information and communication technologies (ICT) are transforming the retail sector with a proliferation of new channels and virtual alternatives. This change is observed in spending patterns: online retailing in the UK accounted for 14% in 2014 of all sales in 2014 up from 2.1% in 2002, Office for National Statistics The remainder of this paper is organised as follows. In the next sub-sections, we briefly review earlier studies on ICT’s impact on shopping related personal travel and present specific objectives and rationale behind using hazard-based models as well as our focus on grocery shopping. In the following sections, we lay out the methodology describing analysis methods and empirical data used, followed by presentation of the results and conclusions.At a conceptual level, transport researchers classified potential implications of ICT on personal travel into four types: substitution, complementarity, modification, and neutrality Salomon . BuildinA common challenge is finding suitable datasets as national and regional travel surveys often capture very limited information regarding online activity and are subject to substantial local variation and idiosyncrasy. Circella and Mokhtarian  and Cao Against this background, the overall aim of the present study is to investigate the effects of online shopping on the temporal patterns of shopping activity and related travel demand by making use of hazard models. Hazard based models have been previously applied to analyse inter-shopping duration for traditional in-store shopping trips  inter-shopping duration for all types of shopping events (including both online and in-store activity) and (ii) duration between in-store shopping trips  generating personal travel to stores.Modelling the duration between consecutive shopping episodes including both online and in-store activity will contribute to multi-day activity generation work for estimating travel demand. It will also help explore the effects of online shopping on frequency and trips generated, potentially providing new insights to the complementarity or substitution question. It will also contribute to the development of tools that enable predicting when the next shopping event or trip will take place. Such prediction capability is crucial for retail delivery operations especially in certain market segments such as online groceries given their struggle to make businesses profitable (Twentyman The UK has a comparatively developed online market for groceries (Kantar Worldpanel Data used for the present study were obtained from a consumer panel run by Kantar Worldpanel (KWP). Participating households use hand-held optical scanners to record daily purchases of fast moving consumer goods that are brought home. Fast moving consumer goods include products found in supermarkets typically bought frequently and at relatively low prices. Examples are groceries, toiletries, health and beauty items. Panellists are also asked to scan and send till receipts whenever they make a shopping trip or get deliveries. Shopping occasions are recorded regardless of the retail chain, hence include visits to smaller local shops, independent corner shops, and larger supermarket chains. KWP is a continuous panel where households can participate for as long as they wish providing longitudinal data and participants receive incentives in the form of redeemable points. Household characteristics including socio-demographics are collected at the initial interview and continuously updated every six-months or annually. All household members record their purchases separately, however the dataset employed had an indicator for main shopper only but otherwise did not distinguish between other household members. KWP defines main shoppers as household members that are responsible for the bulk of grocery shopping in their household. For model estimations, we use shopping occasions recorded by all shoppers in the household without distinguishing between different members of the household. Purchases from all retailers including online retailers are recorded together with basket sizes in terms of monetary value. Unlike travel surveys, both online and in-store shopping observations contain data at the same level of detail. Shopping records include visits where a transaction occurs since product level purchases are recorded, hence will exclude search only or returns only visits. Since the focus is on grocery shopping, however, shopping occasions which will not involve any purchases are likely minimal. Information on basket sizes is also crucial as the amount of shopping will also potentially influence the duration until the next shopping occasion. For assessing the influence of online shopping on inter-shopping duration, it is important to separately account for basket size effects especially since online shopping is often associated with large basket sizes due to minimum size requirements for delivery. Consumer panel data is also attractive as market research companies operate consumer panels in many countries and some make it available to researchers.The sample obtained from KWP covers a one year period between September 2013 and August 2014 from a sample of 168 households in London. 124 households in our analysis sample are panellists who reside in the two selected boroughs, Barnet and Enfield. Thirty four out of 124 were online shopping households with reported online observations during the one year period. An additional forty four households were drawn randomly from London among online shopping households since we are primarily interested in their behaviour. This, however, causes sampling bias as online shopping households are over represented in our estimation sample. To correct for this, we use weights for all observations assuming that the share of online shopping households in London matches observed shares in Enfield and Barnet.While non-traditional panel data offers significant advantages for research, potential problems and sampling biases should not be overlooked. We note that our sample will share important characteristics relating to the geographical proximity of residential addresses. Also, while the number of recurring observations from each responding household was large, the main limitation is that the number of households in the sample was relatively small due to budget constraints. If population scale prediction is a prioriry, then a larger and more representative sample would be desirable. Here, we demonstrate the insights drawn and prediction capabilities that can be developed with existing data sources using modelling tools as presented below.Hazard-based methods have been initially developed for modelling duration data such as time to failure or time to some form of state change. These methods are often used in survival analysis in the context of biological problems  and reliability analysis for mechanical systems. Hensher and Mannering ; Bhat ant given that it has lasted until t is described by the hazard function h(t). Estimating effect sizes associated with selected determinants of duration such as demographic variables and situational factors are of interest for studying inter-shopping duration behaviour. In the Cox proportional hazards model, it is assumed that covariates act multiplicatively on an underlying hazard function, which can be represented as in Eq.  will take place at time s in Eq. . Note ths in Eq. .1\documei and are assumed to follow a Gaussian distribution. Additionally, random effect terms capture the influence of unobserved risk factors i.e. omitted variables affecting the hazard. While only few risk factors can be observed and meaningfully measured, other unknown or unmeasured variables may influence the time between shopping occasions. Modelling individual unobserved random effects does not inform on specific omitted variables , but highlights that some significant factors have been excluded  and travel for shopping (inter-shopping-trip durations). We do so by incorporating, along with other shopper characteristics and situational variables, two key indicators: (i) whether the household have adopted online shopping as a channel; and (ii) whether their last shopping was online. The former is a dummy variable and is equal to one only after a respondent is observed shopping online and remains equal to one for the remainder of our observation period.Specification search was conducted using household characteristics and basket size in terms of monetary value. The panel collects information on income, but panellists are not required to report this information. Income information was missing for the sig of the households in the dataset we were provided with. Therefore, social class was used as a proxy for income where higher social classes are assumed to be associated with higher income bands.We estimated hazard models separately for (i) inter-shopping-event durations and (ii) inter-shopping-trip durations as shown in Tables Estimation results for inter-shopping-event durations using the fixed effects only proportional hazard model Table  show incFor inter-shopping-trip duration models Table , househoCrucially, having shopped online since the last shopping trip significantly reduces the likelihood of a physical shopping trip. This effect becomes even stronger in the frailty model. We do not observe the same effect for inter-event durations. Hence, shopping online does not have a significant effect on overall shopping activity frequency, yet affects shopping trip rates. This is a key finding and suggests potential substitution between online shopping and physical trips to the store. In line with intuition, when households order their groceries online it delays the next physical trip for in-store shopping. It therefore suggests that online shopping activity might affect trip rates.This paper presented the use of consumer panel data and hazard based duration models to explore the potential impacts of online shopping separately on shopping trip frequency and overall shopping activity patterns. Results provide new insights to substitution or complementarity question. Additionally, methods presented can be used for predicting next online order or shopping trip, which is crucial for activity generation models used for travel demand predictions and also for delivery operations. Our study has a number of novel components in comparison with past work that focused on understanding the implications of wider use of ICT on personal travel.First, while transport researchers have used hazard based duration models to analyse inter-shopping duration in the context of multi-day activity generation, they have not considered online shopping activity and its effects on overall activity generation. Our study accounts for the influence of online activity on temporal patterns of shopping activities.Second, our analyses are based on a dataset of unprecedented richness in transport research with respect to capturing both online and physical shopping activities. In consumer panels, online shopping activity data are collected in an episode-based manner, rather than through retrospective questionnaires where respondents report how frequently they shop using a points scale. This enables development of more advanced models to help us better understand changes in behaviour triggered by ICT use. Additionally, shopping basket characteristics, likely to affect shopping behaviour yet often neglected in transport literature, are available and used in empirical estimations. Importantly, market research companies operate consumer panels in many countries and make it available to researchers. This is crucial for the generalisability of our proposed method.Third, we differentiate between shopping events and shopping trips, with the former referring to all types of shopping activity including both online and in-store and the latter restricted to physical shopping trips. Separate models were estimated for each, and results suggest potential substitution effects between online and in-store shopping potentially affecting trip rates. We find that online grocery shopping episodes increase inter-shopping-trip durations and do not significantly influence inter-shopping-event durations. These conclusions are specific to grocery shopping and it is possible that use of ICT has different implications, for instance, on non-maintenance shopping. Future work might therefore focus on obtaining specifically rich datasets enabling similar analyses for other types of shopping.We finally would like to emphasise that our analyses demonstrated the practical use in transport studies of non transport datasets that are becoming increasingly available. Apart from consumer panels operated internationally (similar to that used here), researchers in marketing and retailing already work with data from online retailers, credit card transactions, and loyalty cards. Desirable collaborations between transport and retail researchers is crucial to unveil the value of existing data sources for transport research.


To differentiate normal adaptive responses ("benign") from abnormal onesremains a challenge. Here we address some important issues related to the discussion oncardiac remodeling in exercise, recently revisited by Vidaletti-Silva andcolleagues2 and also ofventricular arrhythmias,3 which mayresult in undesirable events.4In terms of morphological adaptations, the left atrial and ventricular hypertrophy callattention due to their potential association with the onset of supraventriculartachyarrhythmias5"However, mounting evidence has been suggesting that the remodeling response due toexercise training load  may notconfigure a state of disease - i.e., the "physiological but nor pathological"remodeling.6 - an increase ofthe left cavities' volume for those overloaded by the cardiac output ; or the hypertrophy of the left ventricle (LV) septum for those overloaded byblood pressure levels . As a minor comment, theMorganroth hypothesis has been recently revisited after the observation of cases ofseptal hypertrophy in endurance athletes.7With a focus on the left chambers, it is known that the blood pressure and the volumetricoverload may result in two classical morphological characteristics, accordingly to theMorganroth hypothesis1 have addressed the question ofdifferences in cardiac remodeling due to sports modalities through a cross-sectional,comparator-group design, comparing endurance athletes  andstrength-trained athletes  - two classes and levels of modalitiesthat seem appropriate for this comparison. In their findings, no moment-differencesbetween groups were observed for the LV mass, when adjusted for their surface area. Asexpected, septal and posterior LV thickness were different between endurance andstrength athletes, but not the LV end-diastolic volume. The vascular function  was also evaluated and nodifferences were found. The take-home message of this study, at least in light of ourinterpretation, is that athletes in a range of 5 to 7 years of training have adaptationsno bigger than the established thresholds for normality for LV dimensions8 and wall thickness.9Although well-established in scientific literature, Vidaletti-Silva et al.We should acknowledge that, even within borderline values, there were no impairment ofthe systolic and diastolic function of the myocardium in either groups, depicting thenormal adaptive nature of the cardiac structure findings. Even though a simpleexperiment, this cross-sectional study corroborates the hypothesis of different cardiacadaptations due to different training modalities. Finally, to detect some abnormalmorphological adaptations in athletes remains a challenge, especially for those withinborderline values. We welcome studies such as this one - that sheds a light on this grayarea.


Introduction: To establish an alpine ski racing (ASR) specific dryland high intensity training protocol (HIT), we set out to analyze cardiorespiratory and metabolic responses of three ASR specific HIT modes using a ski ergometer compared with a running HIT.Methods: Ten healthy international FIS level subjects (18 ± 1 years) performed an incremental running VO2max test, three different ASR specific HIT modes  and a running HIT with measurements of VO2, heart rate (HR), blood lactate, and rate of perceived exertion (RPE). The HIT protocols included 15 × 1-min intervals with >90% HRmax and 30 s active rest. Furthermore, one elite alpine skier performed an 8-week, 17 session HIT block using the SL/GS mixed mode.Results: Running HIT resulted in greater VO2peak and whole-body RPE compared with the three ASR-specific HIT modes. During all four exercise modes participants were able to reach exercise intensities high enough to be classified as HIT (>90% HRmax and >89% VO2max). Legs RPE was similar between the four HIT modes, while arms RPE was higher for the ski-specific HIT. For all studied parameters, similar results for the three skiing specific HIT modes were observed. The 8-week HIT block was feasible for the athlete and resulted in an 11% increase in VO2max at unchanged peak power output.Conclusion: Across all HIT protocols high cardiorespiratory and metabolic responses were achieved. Therefore, the ASR specific HIT was shown to be feasible, thus could offer new possibilities for endurance training in elite alpine skiers. It is suggested to use the SL/GS mixed mode in terms of movement variety. The reduced VO2 in the ski-specific modifications can be attributed to the concentric and eccentric muscle activity resulting in mechanical hindrance for O2 extraction. The long-term effectiveness of ASR specific HIT in elite alpine skiers needs to be proven in a future study. Alpine ski racing (ASR) consists of competition runs of 45 s  up to 2.5 min  and can be categorized as high-intensity short-term endurance exercise. While technical skiing skills appear to have the greatest effect on performance, the ability to continually exhibit technical competence within a race but also through a long competitive season requires high capabilities within all physiological systems . In thismax; e.g., with respect to maximal HR values achieved during incremental tests to exhaustion with running or in comparison to the theoretical calculated value based on the equation 220-age) are typically attained by the end of the race in either of the four ski disciplines SL, Giant Slalom (GS), Super-G and Downhill (2peak) reached during a run  values (88.9–102.5% of HRDownhill . Howeverng a run  with docng a run  up to 10ng a run . The mosciplines .2max with 4.3–6% (High intensity training (HIT) was demonstrated to be a time efficient alternative to traditional continuous endurance training , inducinh 4.3–6% . It shouIn high performance sports, it has been suggested that improving in the quality of training is more effective in enhancing performance than just increasing the quantity of training. Several studies have suggested that testing  as well max and VO2 values >84% VO2max) were possible , and (3) test the feasibility of a specific HIT block over 2 months with 17 training sessions as a preparation for the Pyeongchang Winter Olympics 2018 as a pilot study. We hypothesized that (a) with the ASR specific HIT protocols the intensities complying for HIT are possible and (b) with HIT using running higher physiological response will be achieved compared with the ASR specific HIT concepts.Therefore, the aims of the current study were threefold: (1) to develop different ASR specific dryland HIT protocols on a commercially available ski ergometer and to compare these with a running HIT session using physiological parameters and rating of perceived exertion (RPE); (2) determine the ski specific HIT mode, that complies best with the requirements of a HIT  level. Participants and their parents were fully informed about the study details and participation requirements with written and verbal information before providing written informed consent to participate. The study received approval from the local Ethics Committee and was conducted in accordance with the Declaration of Helsinki. One participant was not able to perform all test trials based on a meniscal injury during ASR training within the period of the study.Ten male junior alpine skiers were recruited from a regional Ski Gymnasium to take part in the study. Participants’ characteristics are presented in 2max test running on a 400-m level outdoor track, (2) a familiarization HIT session on the ski ergometer for each of the three simulated skiing modes , and (3) the four HIT sessions with running, GS, SL and GS/SL mixed in randomized order on four separate days with a minimum of 48 h in between. During the VO2max test and each HIT session VO2, HR, blood lactate, RPE  for the whole body (RPEwhole-body), legs only (RPElegs), and arms only (RPEarms) were recorded. For standardization purposes, food intake was not permitted 4 h prior to testing and participants were instructed not to change their diet and amount of physical activity throughout the examination period. Furthermore, for all testing days, participants were asked to report well-hydrated and to refrain from consuming alcohol and engaging in strenuous exercise at least 24 h prior to testing.Following the recruiting process every participant underwent six visits on separate days within 2 weeks during the conditioning period (June-July): (1) a VOA portable ski ergometer was employed for the ASR specific dryland imitation. The ergometer is based on a commercially available simulator . The ergometer is equipped with six elastic bands that can be used for regulating the load during the exercise. The basic unit was reinforced to resist the high mechanical stress and assembled with a custom-manufactured slide board. The slide board was modified with an alpine ski binding to train more ski specifically. The bindings were mounted on a plate which served to lift the respective “inside heel” in order to enable ski specific knee and hip angulation . CompareFigure 1.The ski-specific motion sequences on the ski ergometer were adapted to the typical on-snow SL and GS techniques based on a pilot study of 2max test was performed on a level 400-m outdoor track. Each subject performed a standardized 10-min warm-up at a running speed of 8 km h-1. Subsequently the test protocol started with a speed of 9 km h-1 and a 1 km h-1 increment every 30 s until exhaustion. Termination criteria were either physical exhaustion, or no longer being able to keep up the running speed of the stage. Running speed was provided by a cyclist driving on the side of the runner. VO2 and HR were measured continuously and a lactate sample was taken during the first, third, and fifth minute upon completion of the test. VO2max, HRmax, peak blood lactate, and peak running speed were determined. This test concept was not separately validated, but is a standard test that is generally applied at our institute for outdoor field tests for establishment of VO2max in various sports   e.g., .max. Participants warmed up running on the track for the running HIT protocol, and cycling on a cycle ergometer for the ski-specific HIT protocols. Each HIT session consisted of 15 bouts of 1 min each, with 30 s of low intensity active breaks, with the goal being to reach an intensity of >90% HRmax as quickly as possible. The 1-min interval duration was chosen in accordance with the mean run durations of the technical disciplines SL and GS (2max test) in combination with HR values (target HR of 90–95% HRmax). Participants walked during the 30-s breaks. To control HR intensity, participants were instructed to reach a HR of 90–95% HRmax as quickly as possible. For the ASR specific HIT protocols on the ski-ergometer, the resistance provided by the number of rubber bands used was determined during the familiarization day. As criteria served the highest possible amount of rubber bands during the familiarization day the athlete could compete during repeated 1-min bouts. The 30-s breaks were performed with relaxed side-to-side bouncing on the ski-ergometer in an upright position. VO2 and HR were measured continuously throughout the HIT protocols. Blood lactate was sampled after the 5th, 10th, and 15th interval and in the third and fifth minute post completion of the HIT protocol. Finally, RPE values for the whole-body, legs and arms were recorded upon completion of the training.Each of the four HIT sessions began with a 10-min warm-up with an intensity of 70% HRL and GS , and alsL and GS . For the2 was continuously recorded by a portable breath-by-breath metabolic cart . The athletes were fitted with a proper sized mask covering the mouth and nose . Prior to each test trial the gas analyzer’s oxygen (O2) and carbon dioxide (CO2) sensors were calibrated using a two-step calibration procedure with ambient air conditions (20.93% O2 and 0.03% CO2) and the anticipated expiratory gas percent using calibration gas containing 15% O2 and 5% CO2  (rest volume: nitrogen). The flow volume was calibrated using a 3-L syringe. Both calibration procedures were performed directly before each test. Participants’ HR was recorded by telemetry  sampling at 1-s intervals. For lactate analysis, a 20 μl capillary blood sample from the finger-tip was collected and quantified using an amperometric-enzymatic technique . The lactate sensor was calibrated before each test using a lactate standard sample of 12 mmol L-1. Results within a range of ±0.1 mmol L-1 were accepted.VO2max ramp protocol was performed on a cycle ergometer  before and after (at the end of the second recovery week) the training period. The workload was set at 50 W with a 30 W increase every 30 s until exhaustion. VO2 was measured with a breath-by-breath spirograph as described above.In a single case study during the conditioning phase (June and July), the feasibility and effects on aerobic capacity of an 8-week HIT block using the ASR specific HIT protocol on the ski-ergometers preparation for the 2018 Olympics was analyzed. One elite AS athlete  volunteered to take part. A VOmax, followed by the HIT protocol (15 × 1 min at > 90% of HRmax with 30-s recovery) alternating between the SL and GS mode between the bouts and a 10-min cool-down on the bicycle ergometer or running. Within each session HR and blood lactate values were collected .The training period consisted of two blocks of three training weeks with three HIT sessions/week (first week with only two HIT sessions) interspersed with one recovery week (only one HIT session). In total, the athlete performed 17 HIT sessions. The athlete was instructed to maintain his strength and coordination training during the intervention period. All of the HIT sessions included a 10 min warm-up on a bicycle ergometer at an intensity of 70% HRpost hoc analysis. To compare the progression of the HR, VO2 and blood lactate values across the 15 intervals between the four HIT modes a 3 × 4 ANOVA with repeated measures  was performed. Alpha level of significance was set to 0.05. In addition, the values obtained were evaluated by calculating the effect size (pη2) and statistical power. The Statistical Package for the Social Sciences  was used for statistical analysis.All data exhibited a Gaussian distribution verified by the Shapiro–Wilk test and accordingly, the values are presented as means (±SD). A one-way ANOVA (four HIT protocols) was performed for each dependent variable with Bonferroni 2max of 57.7 ± 3.7 ml min-1 kg-1 (range: 50.8–62.7) with a HRmax of 199 ± 8.4 bpm (189–216), and peak blood lactate values of 11.1 ± 1.0 mmol L-1 (8.4–13.4).During the baseline running ramp protocol participants reached a VOTable 2. The running HIT achieved higher physiological response in some of the measured variables in comparison to the ASR specific HIT modalities. The main differences were found with respect to cardiorespiratory parameters with higher mean VO2 values in the running HIT protocol compared with all three specific HIT modes (P = 0.008). With respect to VO2peak values, running HIT was higher compared with HIT in GS (P < 0.001) and SL (P < 0.01), while no difference was found to the mixed GS/SL mode. Peak HR trended toward being lower in the GS/SL mixed HIT than the running HIT, although statistical power was low, while no differences were found for mean HR values. Peak blood lactate values was lower with HIT in GS compared with the running HIT (P < 0.05). RPE for the whole body was higher in the running HIT when compared with the SL and mixed GS/SL HIT mode. RPE arms was higher in GS and GS/SL mixed mode compared with the running HIT. RPE for the legs was not different between all four HIT modes.The comparison among the four HIT protocols is presented in 2 and blood lactate values across the 15 1-min intervals within each HIT session is presented in Figures 4. Interaction effects for time x HIT mode were found for VO2 (P = 0.029) and blood lactate (P = 0.001) and with a more pronounced increase across the training session in the running HIT compared with the ASR specific HIT protocols.An illustration of the evolution of HR, VOFigure 5 illustrates the development of HR values across the 17 HIT sessions within the 8 weeks training period. All the HIT sessions could be easily performed by the athlete and he was able to reach in all the training sessions a HR > 90% HRmax, mostly after the 10th interval. Peak blood lactate was 8.1 ± 1.3 mmol L-1 (range: 6.5–11.6) across the 17 training sessions. Following the HIT intervention the VO2peak was increased by 11%  and the peak power output during cycling remained constant at 530 W.max, >88% VO2max, blood lactate > 5.9 mmol L-1); (2) physiological response with respect to VO2 values was higher in the running HIT compared with the three ASR specific HIT modes; (3) the three ASR specific HIT modes did not differ with respect to the analyzed physiological and RPE values; (4) RPE for the whole body was higher during the running HIT when compared with the specific HIT SL and HIT GS/SL; (5) RPE for the arms was more pronounced in the three ASR specific HIT modes compared with running HIT while no difference was found for RPE legs; and (6) a pilot study in one participant using an ASR specific HIT program over 8 weeks was shown to be feasible and led to an 11% improvement in VO2max with unchanged peak power output during a cycling ramp protocol.The main findings of the current study are: (1) all four HIT protocols induced sufficient physiological loading to be quantified as HIT , peak blood lactate (GS), and whole-body RPE (SL and GS/SL mixed). However, all four HIT protocols still reached clearly the intensity criteria for being classified as HIT . In addition, the intensity during the specific HIT protocols on the ski-ergometer was comparable with reported values achieved during actual ASR on-snow training and competition. As stated earlier, %VO2max values of 64–100% and %HRmax values of 89–102% are documented during ASR (max and 88–91% VO2max) and participants were able to maintain the intensity across the 15 intervals of each HIT protocol . Most likely, these high values during the specific HIT modes can just be attained if high strength and coordinative capacities of the athletes are already developed. As demonstrated during ASR, these are the prerequisites of elite alpine athletes to enable them to ski in a very active and exhausting skiing style . The interaction effects demonstrated that this rise was lower within the first 10 intervals. Therefore, the initial intervals within the ASR specific HIT modes need to be more intense, but merits further analysis.Except for one significant difference in peak HR between GS/SL mixed HIT vs. running HIT no clear differences in HR could be detected between the four HIT modes. However, this significant difference needs to be assessed critically based on the low statistical power. Based on the high effect size it can be assumed that with a higher sample size the running HIT might have led to higher physiological load also with respect to HR compared with the ASR specific HIT modes. VOremities  with botremities . In contremities ,b, 2017.c motion . This atWith respect to the subjective loading of the four HIT protocols, it was found that the legs were equally loaded in all HIT protocols. Whole body RPE was highest during the running HIT, and especially greater compared with the SL and SL/GS HIT modes.In a study of fit and unfit recreational skiers it was demonstrated that the subjective loading of the legs during alpine skiing was even greater when compared with classical endurance exercises like cross-country skiing and cycling ,b, 2017 The use of the arms during the ski ergometer exercise led to increased arm RPE when compared to the running HIT. The athletes were instructed to hold the handle bars with their hands in order to freeze the upper body in the center of the device. By doing so a simulation of representative lean angles and accompanying knee and hip angulation was possible . TherefoConsequently, the ASR specific ski-ergometer exercise described in the current study might constitute a good combination to specifically train HIT, but also to specifically load and train important structures and muscles for ASR with respect to performance  but also specific injury prevention (core stability). Future research is needed to prove this concept on effectivity in enhancing ASR performance.2 was higher and whole-body RPE lower in the GS/SL mixed mode than the GS or SL HIT. Based on this outcome, as well as the feedback from athletes preferring less monotonously sessions, the GS/SL mixed HIT protocol was applied for a single case pilot training study in one elite ASR skier to check if this training concept is feasible for ASR elite sports. The results demonstrate that the athlete was able to perform all 17 sessions with sufficient physiological response , with no marked signs of overloading symptoms. The training led to an 11% increase in the VO2max and unchanged peak power output on the cycle ergometer. Based on these findings, a future study is warranted demonstrating if the implementation of a specific HIT over a longer period of time is effective in increasing aerobic and anaerobic capacity, peak power output and specific strength of the lower body and the trunk when compared with a standard HIT training concept in running or cycling.All specific HIT modes led to comparable physiological and metabolic loading, whether cycle frequency was high  or low  or if these two modes were alternately applied during each consecutive interval (GS/SL mix). Though not statistically significant, VO2 compared with the three ASR specific HIT modes. However, with all four HIT protocols participants were able to reach exercise intensities sufficiently high to be classified as HIT (>90% HRmax and >88% VO2max). The increased loading of the arms during the ASR specific HIT workouts might be of special interest for training both the aerobic and anaerobic capacity but also upper body and trunk strength, all important aspects or performance and injury prevention in ASR. Consequently, the combination of the ASR specific ergometer with a 15 × 1-min HIT protocol might provide sufficient stimulus for the cardiorespiratory and metabolic systems to enhance aerobic and anaerobic capacity. The effectiveness of such a HIT protocol over longer duration was shown to be feasible in one elite alpine skier. Based on his successful skiing season following this intervention , no negative side-effects on true skiing capabilities can be stated so far. However, the effects of this training protocol on a larger group of elite alpine skiers on aspects of endurance, power and core needs to be proven in a future study. Furthermore, a detailed description of the functional  similarity between the instructed movement on the ski-ergometer and the on-snow situation would complete the picture on how the ergometer could be used best possible in the off-season training of ASR athletes.The HIT protocol with running resulted in a more pronounced response in VOTS, JK, RH, MC, and EM conceived and designed the experiments, and read and approved the final manuscript. JK, RH, and MC performed the experiments. TS, RH, and MC analyzed the data. TS, JK, and RH prepared the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.