Background: Pulsed field ablation [PFA] is a novel ablation technique for pulmonary vein isolation [PVI] in patients with paroxysmal and persistent atrial fibrillation. However, data for the efficacy and safety of PFA for left atrial substrate modification using a single shot PFA system, in patients with long-standing persistent atrial fibrillation [AF] and left atrial macro- as well as micro-reentrant atrial tachycardia [LAMRT], are scarce. Here, we provide a small, single-center case series regarding the efficacy and safety of left atrial substrate modification using a single-shot PFA system. Methods: Nine patients with long-standing persistent AF and LAMRT underwent redo-PVI and left atrial substrate modification using a single-shot PFA system. Patients were subsequently followed up for 1 year. Results: The median age was 64 years [IQR 55.5–75], with 44% of the participants being female. The median time since the first diagnosis of AF was 7 years [IQR 4–15.5]. After re-PVI, posterior wall isolation was performed in five patients, roof isolation in six patients, and anterior wall ablation between the superior mitral annulus and the right superior pulmonary vein [RSPV] in five patients. In two patients, cavotricuspid isthmus ablation was additionally performed to treat typical atrial flutter. The acute procedural success rate was 100%, with all LAMRTs and typical flutters successfully terminating by ablation. At 1-year follow-up, four patients [44%] experienced a recurrence of any atrial arrhythmia. Median time to recurrence was 164 days [138–212.8]. Importantly, no acute or chronic complications were observed. Conclusions: In this small, single-center case series, left atrial substrate modification for long-standing persistent AF and AT using a single-shot PFA system was safe and showed an excellent acute success rate.

Left atrial (LA) fibrosis is a significant contributor to the pathophysiology of atrial fibrillation (AF) and a well-known predictor for arrhythmia recurrence post ablation. LA epicardial adipose tissue (EAT) plays a role in cardiac metabolism, can influence local inflammation and is associated with AF. Recent data suggests that beside LA EAT volume, its status of inflammation, as identified by higher values of attenuation, plays a significant role in the development and maintenance of AF as well. However, data on the association of LA EAT and LA fibrosis are scarce. To evaluate the correlation of LA EAT volume and inflammation with LA fibrosis in patients presenting for first time AF ablation of symptomatic AF. Consecutive patients presenting for first time AF ablation were included. All patients underwent computed tomography one day prior to the ablation procedure. LA area was manually traced and surrounding tissue within 1 cm of the LA, with Hounsfield units (HU) ranging from -195 to -45, was identified as EAT. For identification of study subjects with inflammatory LA EAT changes, the study population was divided by the median HU value. All participants underwent high density mapping of the LA in sinus rhythm for evaluation of general bipolar voltage and for identification of areas of low voltage (<0.5mV) prior to AF ablation. Follow-up and outcome data were collected. In total, 107 patients (44% female, age 65±11years, 45% persistent AF) were enrolled. The median LA bipolar voltage and low voltage area were 1.87mV (IQR 0.97-2.70) and 32.63 cm² (IQR 3.98-34.97). Elevated absolute volumes of LA EAT showed a correlation to decreased levels of LA bipolar voltage (r=-0.228; p=0.022) and to increased areas of low voltage (r=0.225; p=0.033). After adjustment for LA volume however, this correlation did not remain significant. Attenuation of LA EAT did not correlate with LA bipolar voltage. After stratification for the median HU value (-91.3), patients with a higher attenuation (≥-91.3 HU) (as a marker for inflammatory changes of the LA EAT) were younger (63±12 vs 68±9 years; p=0.039) and more often male (66 vs 46%, p=0.049), when compared to the study population with lower attenuation (<-91.3 HU). After a median follow up of 13 months (IQR 7-36) 44 patients (41%) experienced arrhythmia recurrence. Patients with higher LA EAT attenuation suffered from a higher rate of arrhythmia recurrence (p=0.030) (Figure 1). Higher tissue attenuation as a sign for LA EAT inflammatory changes did not correlate with LA fibrotic changes in patients presenting for AF ablation but is associated with higher rates of arrhythmia recurrence post ablation, when compared to patients with lower attenuation.

Abstract Background Pulsed field ablation (PFA) is a novel ablation technique for pulmonary vein isolation (PVI) in patients with paroxysmal and persistent atrial fibrillation. However, data for efficacy and safety of PFA for left atrial substrate modification in patients with long-standing persistent atrial fibrillation (AF) and macro- as well as microreentrant atrial tachycardia (AT) is scarce. Aim Here we provide a retrospective, single-centre case series regarding efficacy and safety of left atrial substrate modification, using a single-shot PFA system. Methods and Results Over a period of 6 months, 8 patients with long-standing persistent AF and AT underwent Re-PVI with left atrial substrate modification using a single-shot PFA system. Median age was 63 years (IQR 58 - 75), and 4/8 of patients were female. Time from first diagnosis of AF was 7 years (IQR 4 –10). All but 1 patient underwent previous PVI (IQR 1-3) with (5/7) or without (2/7) prior substrate modification using radiofrequency ablation. On transthoracic echocardiography, all patients showed severe left- and right-atrial enlargement, with LA volume of 58 ml/m2 (IQR 49.7–72) and RA diameter of 62 mm (IQR 55-75). In 8 patients, 9 ATs and 2 typical flutters were treated with PFA. Following PVI, additional posterior wall isolation was performed in 6/8 patients, roof in 6/8, and anterior wall (between superior mitral anulus and RSPV) in 4/8 patients. In addition, 2/8 patients had cavotricuspid isthmus ablation for typical atrial flutter. All patients received atropine prior to PVI, as well as bolus of nitro-glycerine prior to PFA of anterior wall and/or cavotricuspid isthmus. Acute success rate was 100% and all ATs as well as typical flutter terminated with PFA. After median follow-up time of 88 days (IQR 61-112), 3 patients had a documented recurrence of AF/AT, in 2 of which electrical cardioversion was necessary. We observed no acute and/or chronic complications following PFA, i.e. no pericardial effusion/tamponade, TIA/stroke, myocardial infarction, coronary artery spasm, AV-block, bleeding, or atrioesophageal fistula. Conclusion In this small, single-centre case series, left atrial substrate modification for long-standing persistent AF and AT using a single-shot PFA system was safe and showed an excellent acute success rate.

Background: The incidence of atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) is high. Impaired left atrial (LA) function is a major determinant in HFpEF. However, the extent of electrical LA tissue degeneration in HFpEF is unknown. Therefore, we sought to investigate the amount of arrhythmogenic and fibrotic LA tissue degeneration in HFpEF patients presenting for AF ablation. Methods: We prospectively screened consecutive patients presenting for first time AF ablation. The HFA-PEFF score was used to identify HFpEF patients. Bipolar high-density voltage mapping was created in sinus rhythm prior to ablation to evaluate the general LA bipolar voltage and quantify areas of low voltage. LVAs were defined as areas with bipolar voltage < 0.5 mV. Results: In total, 187 patients were prospectively enrolled (age 65 ± 11 years, 45% female, 46% persistent AF, 25% HFpEF) in this study. HFpEF patients were older and had a higher CHA2DS2-VASc score (70 ± 9 vs. 63 ± 11 years and 3.2 ± 1.5 vs. 2.3 ± 1.5, each p < 0.001, respectively). Overall, low-voltage areas (LVAs) were present in 97 patients (52%), whereas 76% of the HFpEF population had LVA, as compared to 44% of patients without HFpEF (p < 0.001). HFpEF was associated with generally decreased LA bipolar voltage (1.09 ± 0.64 vs. 1.83 ± 0.91 mV; p < 0.001) and predictive of the presence of low-voltage areas (76% vs. 44% p < 0.001). The HFA-PEFF score inversely correlated with LA bipolar voltage (=−0.454; p < 0.001). Conclusions: HFpEF closely relates to generally decreased LA bipolar voltage and to the existence of fibrotic and arrhythmogenic LA tissue degeneration.

Abstract Background Atrial fibrillation (AF) closely correlates to left atrial (LA) myopathy, which in turn can cause functional mitral regurgitation (FMR). The correlation of LA myopathy to tricuspid regurgitation (TR) is still unknown. Data on the dynamic change of TR post AF ablation is still limited. Purpose We sought to investigate the correlation of LA myopathy to TR and furthermore if TR can be improved by AF ablation. Methods Consecutive patients presenting for first time AF ablation were prospectively enrolled. All patients underwent transthoracic echocardiography at baseline as well as 6 months after the ablation procedure. TR was graded as follows: minimal, mild, moderate and severe (I-IV). All study participants underwent high density bipolar voltagemaps prior to AF ablation to characterize the presence of atrial myopathy. Results Our final study cohort consisted of 143 patients (age 64±11 years, 47% female, 48% persistent AF). 15% had no, 21% minimal, 35% mild, 19% moderate and 9% severe TR, respectively. High density maps with 1325±736 mapping points and with an average bipolar voltage of 1.58±0.89mV were created. A significant decline of average LA bipolar voltage was obvious, when comparing patients without TR to any severity level of TR (p=0.015) (Figure 1), however there was no significant difference in LA bipolar voltage, when comparing different TR severity levels (Figure 1). After a follow up of 6 months a significant improvement of TR was observed (p<0.001) with a median level of improvement by one level. 27% had no, 21% minimal, 31% mild, 18% moderate and 2% severe TR, respectively. Conclusion In patients presenting for AF ablation TR closely correlates with LA myopathy according to decreased levels of LA bipolar voltage. AF ablation results in highly significant TR level improvement.

Background: This study sought to investigate the prognostic impact of right atrial (RA) size and function in patients with heart failure with preserved ejection fraction (HFpEF) in sinus rhythm (SR) and atrial fibrillation (AF). Methods: Consecutive HFpEF patients were enrolled and indexed RA volumes and emptying fractions (RA-EF) were assessed by cardiac magnetic resonance imaging (CMR). For patients in SR, feature tracking of the RA wall was performed during CMR. In addition, all patients underwent right and left heart catheterization and 6 min walk distance (6MWD) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) evaluations. We prospectively followed patients and used Cox regression models to determine the association of RA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death. Results: A total of 188 patients (71% female patients, 70 ± 8 years old) were included. Ninety-two patients (49%) were in persistent AF. Eighty-five patients reached the combined endpoint during a follow-up of 69 (42–97) months. After a multivariate cox regression analysis, the impaired RA reservoir strain (HR 0.949; 95% CI [0.909–0.990], p = 0.016), the RA reservoir strain rate (HR 0.991; 95% CI [0.983–0.999], p = 0.028), the RA conduit strain (HR 0.932; 95% CI [0.879–0.988], p = 0.019), and the RA conduit strain rate (HR 0.989; 95% CI [0.881–0.997], p = 0.011) were significantly associated with a worse outcome for patients in SR. In persistent AF, no RA imaging parameter was related to outcome after a multivariate regression analysis. Conclusions: In HFpEF patients in SR, CMR parameters of impaired RA conduit and reservoir function are associated with dismal cardiovascular outcomes. In persistent AF, RA parameters lose their prognostic ability.

BACKGROUND: Within the presented prospective study, we aimed to illuminate the effect of long-term physical exercise on serum levels of adipsin (complement factor D) and angiopoietin-like 4 (ANGPTL4). Although past studies already outlined the effects of acute exercise, our trial design aimed to depict the development under long-term physical activity conditions.METHODS: Ninety-eight participants were included in the study and were asked to perform eight months of moderate physical activity for at least 150 minutes/week and/or vigorous-intensity exercise for at least 75 minutes/week. According to initial performance and performance gain throughout the study period, four groups were formed and subsequently compared. Blood sampling for the determination of routine laboratory parameters was done at baseline, after 2, 6, and 8 months. Additionally, adipsin and ANGPTL4 serum levels were concurrently quantified using commercially available ELISA kits.RESULTS: The study cohort consisted of 61.2% male participants with an average age of 49.3 +/- 6.7 years. Adipsin and ANGPTL4 were found to be strongly increased by long-term physical exercise. Participants displaying a performance gain of >2.9% throughout the study showed significantly increased serum levels of both biomarkers.CONCLUSIONS: Serum levels of adipsin and ANGPTL4 were closely tied to the individual performance gain of the participating probands. An association of adipsin levels, initial performance, and serum triglycerides was found at baseline. Interestingly, this interrelationship was not detectable after eight months of physical training. This finding might indicate adipsin's involvement in linking triglyceride-balance to individual performance and energy demands in a homeostatic state.

Background: Obesity and associated steatosis is an increasing health problem worldwide. Its influence on post-hepatectomy liver failure (PHLF) and after liver resection (LR) is still unclear.Methods: Patients who underwent LR were investigated and divided into three groups [normal weight: body mass index (BMI) 18.5-24.9 kg/m2, overweight: BMI 25.0-29.9 kg/m2, obese: BMI >= 30 kg/m2] in this retrospective study. Primary aim of this study was to assess the influence of BMI and nonalcoholic steatohepatitis (NASH) on PHLF and morbidity.Results: Of 888 included patients, 361 (40.7%) had normal weight, 360 (40.5%) were overweight, 167 (18.8%) were obese. Median age was 62.5 years (IQR, 54-69 years). The primary indication for LR was colorectal liver metastases (CLM) (n=366, 41.2%). NASH was present in 58 (16.1%) of normal weight, 84 (23.3%) of overweight and 69 (41.3%) of obese patients (P<0.001). PHLF occurred in 16.3% in normal weight, 15.3% in overweight and 11.4% in obese patients (P=0.32). NASH was not associated with PHLF. There was no association between patients' weight and the occurrence of postoperative complications (P=0.45). At multivariable analysis solely major LR (OR 2.7, 95% CI: 1.83-4.04; P<0.001) remained a significant predictor for PHLF.Conclusions: Postoperative complications and PHLF are comparable in normal weight, overweight and obese patients and LRs using modern techniques can be safely performed in these patients.

Abstract Funding Acknowledgements Type of funding sources: None. Aims The prevalence of atrial fibrillation (AF) in heart failure with preserved ejection fraction (HFpEF) patients is high. Impaired left atrial (LA) function is a major determinant in HFpEF. The extent of arrhythmogenic left atrial tissue degeneration in HFpEF patients is unknown. Methods and results We prospectively enrolled consecutive patients presenting for first time AF ablation. Each patient underwent baseline laboratory and transthoracic echocardiography assessment. The HFA-PEFF score was utilized to identify HFpEF patients. Bipolar high density voltage mapping [1213 (825 to 1606) mapping points] was created in sinus rhythm prior to PVI to evaluate the general LA bipolar voltage and quantify areas of low voltage, a well known surrogate for fibrosis and arrhythmogenesis. 160 patients were enrolled (55 % male). 42 patients (26 %) suffered from HFpEF. Low voltage areas (LVAs) were present in 84 patients (53 %). HFpEF was associated with generally decreased LA bipolar voltage (0.95 ± 0.45 mV vs. 1.59 ± 0.91 mV respectively; p < 0.001) (Fig. 1) and predictive for the existence of low voltage areas (81 % vs. 45 % low voltage area positive, respectively; p = 0.006). The HFA-PEFF score inversely correlated with LA bipolar voltage (r = - 0.380; p < 0.001) (Fig. 1). Furthermore, the HFA-PEFF score closely correlated to the extent of LVAs (r = 0.275; p = 0.001) and to the low voltage amplitude of atrial myocardium excluding areas of low voltage (r = - 0.403; p < 0.001). Conclusion HFpEF is highly predictive for generally decreased LA bipolar voltage and for the existence of fibrotic and arrhythmogenic left atrial tissue degeneration.

BACKGROUND: We aimed to investigate predictors for long-term survival of in-hospital patients with medical emergency team (MET) consultation with or without in-hospital cardiac arrest (IHCA) in Austria's largest medical center.METHODS: Data of patients, who needed an intervention of a MET between 01/2014 and 03/2020 were reviewed forRESULTS: In total, 708 MET calls were analyzed. The minimum follow-up was 7 months, the maximum 6.2 years. The main MET indications were circulatory failure (63%) followed by respiratory failure (27.1%), and bleeding events (3.5%). IHCA with subsequent cardiopulmonary resuscitation (CPR) was experienced by 425 (60%) patients. Of those, 274 (64%) reached return of spontaneous circulation (ROSC), and 221 (52%) survived the first 24-hours (median survival: 146 days) and 22.1% the first year. After adjustment for potential confounders, age (P<0.001), time to ROSC (P<0.001), a non-shockable rhythm (P=0.041), chronic kidney disease (CKD, P=0.041), peak lactate levels (P<0.001), and C-reactive protein (P=0.001) were associated with long-term all-cause mortality in IHCA patients in Cox regression analysis. The 283 MET calls (40%) which were due to other reasons than IHCA were associated with a much better 24-hours (93%) and 1-year survival (61.8%). Beside age (P<0.001), the main risk factors associated with mortality in MET patients without IHCA were comorbidities such as chronic obstructive pulmonary disease (COPD, P=0.008), CKDCONCLUSIONS: Patients triggering MET calls have an increased mortality, especially those with IHCA. Predictors of mortality comprise age, comorbidities, and cardiac arrest-related parameters. A better characterization of MET call populations and their outcome might help to improve clinical decision making.

Abstract Aims We sought to study the prognostic impact of right atrial (RA) size and function in patients with heart failure with preserved ejection fraction (HFpEF) in sinus rhythm (SR) vs. atrial fibrillation (AF). Methods and results Consecutive HFpEF patients were enrolled and indexed RA volumes and emptying fractions (RA-EF) were assessed by cardiac magnetic resonance imaging (CMR). For patients in SR during CMR feature tracking of the RA wall was performed (Figure 1). In addition, all patients underwent right and left heart catheterization, 6 min walk test, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) evaluation. We prospectively followed patients and used Cox regression models to determine the association of RA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death. A total of 188 patients (71% female patients, 70±8 years old) were included of whom 96 (51%) were in SR. Eighty-five patients reached the combined endpoint during a follow-up of 72 (33–101) months. After multivariate cox regression analysis adjusted for age, NT-proBNP level, right ventricular ejection fraction and HF functional class, impaired RA strain (Figure 1A) (HR 0.959; 95% CI [0.924–0.996], P=0.024), RA conduit strain (Figure 1A) (HR 0.944; 95% CI [0.898–0.993], P=0.027) and RA conduit strain rate (Figure 1B) (HR 0.990; 95% CI [0.883–0.998], P=0.013) were significantly associated with adverse outcome for patients in SR (Table 1). In persistent AF, no RA imaging parameter was related to outcome after multivariate regression analysis. Conclusions In HFpEF patients in SR, CMR parameters of impaired RA conduit function show the best association with adverse cardiovascular outcome. In persistent AF, RA parameters lose their prognostic ability. Funding Acknowledgement Type of funding sources: None.

Regular physical exercise was found to be associated with an improved immune response in previous studies. RANTES and CD40L play a pivotal role in host defense, and individuals lacking adequate expression are prone to virus and opportunistic infections. A total of 98 participants were enrolled in this study. The probands were asked to perform moderate physical activity, and bicycle stress tests were performed at the baseline and after 8 months of training to evaluate individual performance. RANTES and CD40L were found to be increased by long-term physical exercise. In particular, probands with a performance gain of ≥3% displayed a pronounced elevation of both markers, paired with a decrease in circulating IL6 levels and an improved lipid profile. In summary, we were able to highlight rising levels of serum RANTES and CD40L under the conditions of physical exercise. Taking their role in host defense into account, a conjunction of physical activity and the adaptive immune system could therefore be assumed. Furthermore, low inflammatory profiles in probands with a significant performance gain suggest a modulation through exercise rather than a generalized pro-inflammatory status.

(1) Background: An unhealthy lifestyle is a significant contributor to the development of chronic diseases. Physical activity can benefit primary and secondary prevention. Higher DNase activity is associated with favourable outcomes after cardiovascular (CV) events. In this study, we aimed to investigate the influence of consequent endurance exercise on DNase activity. (2) Methods: 98 subjects with at least one CV risk factor but the physical ability to perform endurance training were included. Individuals performed a bicycle stress test at the beginning and after 8 months to assess physical performance. In between, all participants were instructed to engage in guideline-directed physical activity. Blood samples were drawn in two-month intervals to assess routine laboratory parameters, cell-free DNA (cfDNA), and DNase activity. (3) Results: Prevailing CV risk factors were overweight (65.9%), a positive family history (44.9%), hypertension (32.7%) and smoking (20.4%). Performance changed by 7.8 ± 9.1% after 8 months. Comparison of baseline to 8 months revealed a decrease in cfDNA and an increase in DNase activity. This effect was driven by participants who achieved a performance gain. (4) Conclusions: Regular physical activity might improve CV health by increasing DNase activity and thereby, the capacity to lower pro-inflammatory signalling, complementing measures of primary and secondary prevention.

BACKGROUND: In addition to diagnosing acute myocardial infarction (MI), the electrocardiogram (ECG) may also predict the culprit coronary artery. We aimed to assess the diagnostic accuracy of ECG algorithms predicting the occluded vessel in inferior ST-segment elevation myocardial infarction (STEMI).METHODS: This retrospective cohort study included 300 consecutive patients with inferior STEMI undergoing acute coronary angiography. A new method based on the summation of ST-segment deviations in multiple leads from the first 12-lead-ECG was used to develop algorithms to discriminate between right coronary artery (RCA) and circumflex artery (CX) occlusion. Additionally, older algorithms were reassessed.RESULTS: The RCA was occluded in 235 patients (78%) and the CX in 65 (22%). ST-segment deviations differed significantly between RCA and CX occlusions in leads I, III, aVR, aVL, aVF and V1. ST-segment deviations in lead I showed the highest discriminatory ability of a single lead (area under the receiver operating curve [AUC]=0.77). The summation of multiple leads further increased the discriminatory ability ("IIIII+aVF+aVR+V1:" AUC=0.86; "III-II-I+aVF+V1:" AUC=0.85). The best binary algorithm "III-II-I+aVF+V1>0.1 mV" classified 86% of cases correctly and was better than the best old algorithm (83.3%). The simpler algorithm "III+aVR+V1 >= 0.1 mV" still predicted 85.0% correctly. All algorithms had higher sensitivities for RCA than for CX detection and performed better in right-dominant anatomy. CONCLUSIONS: A new approach summating multiple ST-segment deviations generated ECG algorithms with higher diagnostic accuracy to predict the occluded vessel in inferior STEMI compared to previous studies. These algorithms may facilitate earlier risk stratification for patients at risk of postinfarct complications.

Background: Low levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) were reported in patients with coronary artery disease, heart failure, chronic kidney disease and diabetes mellitus. Soluble cluster differentiation 163 (sCD163) serum levels are related to M2 macrophages, having anti-inflammatory attributes. As sport is well-known for its anti-inflammatory and cardioprotective effects we aimed to investigate the influence of eight months of physical activity on serum sCD163 and sTWEAK levels. Methods: In total, 109 subjects with at least one cardiovascular risk factor were asked to perform endurance training within the calculated training pulse for eight months. Overall, 98 finished the study. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. The cohort was divided into four groups, dependent on their baseline performance and performance gain. sCD163 and sTWEAK were measured at baseline and after two, six and eight months by ELISA. Results: Those participants who had a performance gain of ≤2.9% (mean gain 12%) within eight months showed a significant increase in sTWEAK (group 2: from 133 to 200 pg/mL, p = 0.002 and group 4: from 166 to 212 pg/mL, p = 0.031) and sCD163 levels (group 2: from 255 to 348 ng/mL, p = 0.035 and group 4: from 247 to 288 ng/mL, p = 0.025) in contrast to subjects without performance gain (sTWEAK: group 1: from 161 to 177 pg/mL, p = 0.953 and group 3: from 153 to 176 pg/mL, p = 0.744; sCD163: group 1: from 289 to 256 ng/mL, p = 0.374 and group 4: from 291 to 271 ng/mL, p = 0.913). Baseline sCD163 correlated with erythrocyte count, hematocrit, ASAT and lipoprotein a, the presence of hypertension and a BMI > 30 kg/m2. Conclusion: Regular physical activity leads to a significant increase in sCD163 and sTWEAK levels of up to 37% and 50%, respectively. It is well-known that physical activity prevents or retards the onset and genesis of chronic inflammatory disease. One possible way of how training evolves its beneficial effect might be by modifying the inflammation status using the sTWEAK–sCD163 axis. Brief Summary: Regular physical activity leads to a significant increase in sTWEAK and sCD163 levels. Both factors are diminished in patients with chronic (inflammation-based) diseases, such as coronary artery disease, heart failure, pulmonary artery hypertension, chronic kidney disease and diabetes mellitus. It seems that the amounts of soluble TWEAK and CD163 are essential for a healthy balance and modulation between pro- and anti-inflammatory processes, and regular physical training could use the sCD163–sTWEAK axis to unfold its beneficial effect.

BACKGROUND:In this trial, we analyzed the plasma levels of novel biomarkers that reflect different pathophysiological pathways (sST2: mechanical strain, IGF-BP2: metabolic pathways, suPAR and GDF-15: inflammatory processes) in patients undergoing physical exercise to investigate the effects of training on their plasma concentrations.METHODS:Plasma concentrations of novel biomarkers (sST2, IGF-BP2, suPAR and GDF-15) were analyzed by means of ELISA in patients with stable coronary artery disease (CAD) undergoing four weeks of high- and moderate-intensity training (EXCITE Trial) and in patients with one or more cardiovascular risk factors undergoing eight months of intensive physical exercise (IGF-BP2). Plasma levels of sST2 in patients undergoing eight months of intensive exercise have been published previously by our study group (1.13-fold change, P=0.045).RESULTS:Four weeks of high-intensity exercise training resulted in a statistically significant change in the plasma level of sST2 (1.106-fold change, P=0.0054) and IGF-BP2 (1.24-fold-change, P=0.0165). Eight months of intensive exercise resulted in a significant increase of IGF-BP2 (median 61.2 ng/mL to 80.7 ng/mL, 1.319-fold change, P=0.006).CONCLUSIONS:The significant increase of sST2 after four weeks might be a short-term effect due to the mechanical strain caused by the high-intensity training program, whereas the increase in IGF-BP2 after four weeks and eight months is likely a result of metabolic changes due to physical exercise.

The aim of this prospective study was to investigate the influence of long-term physical activity on biomarkers for myocyte ischemia (heart-type fatty acid-binding protein, H-FABP), matrix remodelling/vascular stress (soluble isoform of suppression of tumorigenicity 2, sST2) and inflammation (soluble urokinase-type plasminogen activator receptor, suPAR). In this prospective observational study 109 subjects were recruited, 98 completed the study. Subjects were asked to perform exercise within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. Twenty-seven subjects with a performance gain <2.9% were excluded. suPAR, H-FABP and sST2 were measured in serum at baseline and after 2, 4 and 8 months by ELISA. We found a significant decrease in H-FABP (1.86 (0.86) to 1.29 (0.98) ng/mL; p<0.01) and a significant increase in sST2 levels (6126 (2759) to 6919 (3720) pg/mL; p=0.045) during the observation period of 8 months while there was no remarkable change in suPAR levels. We interpret the activity-induced decrease in H-FABP as sign of lower subclinical myocardial ischemia and better perfusion, probably due to a more economic metabolization and electrolyte balance. The increase in sST2 might reflect physiological sports-induced vascular stress. As H-FABP and sST2 play an important role in the pathomechanism of ischemic cardiomyopathy (iCMP) further studies should investigate the influence of regular physical activity on these biomarkers in a population of patients with iCMP. Trial registration number NCT02097199.