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Non-invasive assessment of plaque volume and composition is important for risk stratification and long-term studies of plaque stabilisation. Our aim was to evaluate dual-source computed tomography (DSCT) and colour-coded analysis in the quantification and classification of coronary atheroma. DSCT and virtual histology intravascular ultrasound (IVUS-VH) were prospectively performed in 14 patients. 22 lesions were compared in terms of plaque volume, maximal per cent vessel stenosis and percentages of fatty, fibrous or calcified components. Plaque characterisation was performed with software that automatically segments luminal or outer vessel boundaries and uses CT attenuation for a colour-coded plaque analysis. Good correlation was found for per cent vessel stenosis in DSCT (53±13%) and IVUS (51±14%; r2=0.70). Mean volumes for entire plaque and non-calcified atheroma were 68.5±33 mm3 and 56.7±30 mm3, respectively, in DSCT and 60.8±29 mm3 and 55.8±26 mm3, respectively, in IVUS. Mean percentages of fatty, fibrous or calcified components were 28.2±6%, 53.2±9% and 18.7±13%, respectively, in DSCT and 29.9±5%, 55.3±12% and 14.4±9%, respectively, in IVUS-VH. Significant overestimation was present for the entire plaque and the volume of calcified plaque (p=0.03; p=0.0004). Although good correlation with IVUS was obtained for the entire plaque (r2=0.76) and non-calcified plaque volume (r2=0.84), correlation proved very poor and insignificant for percentage plaque composition. Interclass correlation coefficients for non-calcified plaque volume and percentages of fatty, fibrous or calcified components were 0.99, 0.99, 0.95 and 0.98, respectively, and intraclass coefficients were 0.98, 0.93, 0.98 and 0.99, respectively. We found that using Hounsfield unit-based analysis, DSCT allows for accurate quantification of non-calcified plaque. Although percentage plaque composition proves highly reproducible, it is not correlated with IVUS-VH. [ABSTRACT FROM AUTHOR]

Multi-slice computed tomography (MSCT) is a non-invasive modality to visualize coronary arteries with an overall good image quality. Improved spatial and temporal resolution of 64-slice and dual-source computed tomography (DSCT) scanners are supposed to have a positive impact on diagnostic accuracy and image quality. However, quantitative parameters to compare image quality of 16-slice, 64-slice MSCT and DSCT are missing. A total of 256 CT examinations were evaluated (Siemens, Sensation 16: n = 90; Siemens Sensation 64: n = 91; Siemens Definition: n = 75). Mean Hounsfield units (HU) were measured in the cavum of the left ventricle (LV), the ascending aorta (Ao), the left ventricular myocardium (My) and the proximal part of the left main (LM), the left anterior descending artery (LAD), the right coronary artery (RCA) and the circumflex artery (CX). Moreover, the ratio of intraluminal attenuation (HU) to myocardial attenuation was assessed for all coronary arteries. Clinical data [body mass index (BMI), gender, heart rate] were accessible for all patients. Mean attenuation (CA) of the coronary arteries was significantly higher for DSCT in comparison to 64- and 16-slice MSCT within the RCA [347 +/- 13 vs. 254 +/- 14 (64-MSCT) vs. 233 +/- 11 (16-MSCT) HU], LM (362 +/- 11/275 +/- 12/262 +/- 9), LAD (332 +/- 17/248 +/- 19/219 +/- 14) and LCX (310 +/- 12/210 +/- 13/221 +/- 10, all p < 0.05), whereas there was no significant difference between DSCT and 64-MSCT for the LV, the Ao and My. Heart rate had a significant impact on CA ratio in 16-slice and 64-slice CT only (p < 0.05). BMI had no impact on the CA ratio in DSCT only (p < 0.001). Improved spatial and temporal resolution of dual-source CT is associated with better opacification of the coronary arteries and a better contrast with the myocardium, which is independent of heart rate. In comparison to MSCT, opacification of the coronary arteries at DSCT is not affected by BMI. The main advantage of DSCT lies with the heart rate independency, which might have a positive impact on the diagnostic accuracy. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate radiation exposure of a chest pain protocol with ECG-gated dual-source computed tomography (DSCT). An Alderson Rando phantom equipped with thermoluminescent dosimeters was used for dose measurements. Exposure was performed on a dual-source computed tomography system with a standard protocol for chest pain evaluation (120 kV, 320 mAs/rot) with different simulated heart rates (HRs). The dose of a standard chest CT examination (120 kV, 160 mAs) was also measured. Effective dose of the chest pain protocol was 19.3/21.9 mSv (male/female, HR 60), 17.9/20.4 mSv (male/female, HR 80) and 14.7/16.7 mSv (male/female, HR 100). Effective dose of a standard chest examination was 6.3 mSv (males) and 7.2 mSv (females). Radiation dose of the chest pain protocol increases significantly with a lower heart rate for both males (p = 0.040) and females (p = 0.044). The average radiation dose of a standard chest CT examination is about 36.5% that of a CT examination performed for chest pain. Using DSCT, the evaluated chest pain protocol revealed a higher radiation exposure compared with standard chest CT. Furthermore, HRs markedly influenced the dose exposure when using the ECG-gated chest pain protocol. [ABSTRACT FROM AUTHOR]

Abstract Background Cardiac allograft rejection and vasculopathy are the main factors limiting long-term survival after heart transplantation. In this pilot study we investigated whether non-invasive methods are beneficial to detect cardiac allograft rejection (Grade 03 R) and cardiac allograft vasculopathy. Thus we compared multi-slice computed tomography and magnetic resonance imaging with invasive methods like coronary angiography and left endomyocardial biopsy. Methods 10 asymptomatic long-term survivors after heart transplantation (8 male, 2 female, mean age 52.1 ± 12 years, 73 ± 11 months after transplantation) were included. In a blinded fashion, coronary angiography and multi-slice computed tomography and ventricular endomyocardial biopsy and magnetic resonance imaging were compared against each other. Results Cardiac allograft vasculopathy and atherosclerosis were correctly detected by multi-slice computed tomography and coronary angiography with positive correlation (r = 1). Late contrast enchancement found by magnetic resonance imaging correlated positively (r = 0.92, r2 = 0.85, p < 0.05) with the histological diagnosis of transplant rejection revealed by myocardial biopsy. None of the examined endomyocardial specimen revealed cardiac allograft rejection greater than Grade 1 R. Conclusion A combined non-invasive approach using multi-slice computed tomography and magnetic resonance imaging may help to assess cardiac allograft vasculopathy and cardiac allograft rejection after heart transplantation before applying more invasive methods.

Background: Cardiac allograft rejection and vasculopathy are the main factors limiting long-term survival after heart transplantation.In this pilot study we investigated whether non-invasive methods are beneficial to detect cardiac allograft rejection (Grade 03 R) and cardiac allograft vasculopathy. Thus we compared multi-slice computed tomography and magnetic resonance imaging with invasive methods like coronary angiography and left endomyocardial biopsy.Methods: 10 asymptomatic long-term survivors after heart transplantation (8 male, 2 female, mean age 52.1 +/- 12 years, 73 +/- 11 months after transplantation) were included. In a blinded fashion, coronary angiography and multi-slice computed tomography and ventricular endomyocardial biopsy and magnetic resonance imaging were compared against each other.Results: Cardiac allograft vasculopathy and atherosclerosis were correctly detected by multi-slice computed tomography and coronary angiography with positive correlation (r = 1). Late contrast enchancement found by magnetic resonance imaging correlated positively (r = 0.92, r2 = 0.85, p < 0.05) with the histological diagnosis of transplant rejection revealed by myocardial biopsy. None of the examined endomyocardial specimen revealed cardiac allograft rejection greater than Grade 1 R.Conclusion: A combined non-invasive approach using multi-slice computed tomography and magnetic resonance imaging may help to assess cardiac allograft vasculopathy and cardiac allograft rejection after heart transplantation before applying more invasive methods. [ABSTRACT FROM AUTHOR]

Aims: Detecting stenoses of coronary arteries with multidetector row computer tomography (MDCT) is a well feasible non-invasive method. However, there is still the problem of deciding whether a stenosis is hemodynamically relevant or not. Objective of the present study was to validate the feasibility of a low dose protocol for MDCT using 80 kV for detecting late enhancement. Methods and Results: Using a Alderson-Rando Phantom evaluation of the effective dose of this LE protocol was performed. Ten patients (six male, four female, mean age 61) with known coronary artery disease and scheduled for a conventional coronary angiogram in our facility were subsequently recruited. All patients underwent CT-angiography (CTA) 1 day prior to magnetic resonance imaging. Five minutes after the application of 100ml contrast agent for the CTA scan, a low dose late enhancement scan (80 kV, 400 mA s maximum, ECG pulsed scan, 64 mm x 0.6mm collimation, 0.33 s tube rotation) was performed. Phantom dose measurements showed an effective dose for this protocol of 1.19 mSv (male) and 1.61 mSv (female). Fifty-six percent (5/9) of the patients showed a late enhancement on the MRI scan. Three transmural late enhancements and all four negative findings were correctly identified by CT. This represents a sensitivity of 78% (3/5), specificity of 100% (3/3), NPV of 100% (4/4) and a PPV of 97%. Conclusion: We were able to show that the low dose protocol is feasible and, furthermore, preliminary results look promising. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluates the diagnostic performance of artificial intelligence (AI)-based coronary computed tomography angiography (CCTA) for detecting coronary artery disease (CAD) and assessing fractional flow reserve (FFR) in asymptomatic male marathon runners., Material and Methods: We prospectively recruited 100 asymptomatic male marathon runners over the age of 45 for CAD screening. CCTA was analyzed using AI models (CorEx and Spimed-AI) on a local server. The models focused on detecting significant CAD (≥ 50% diameter stenosis, CAD-RADS 3, 4, or 5) and distinguishing hemodynamically significant stenosis (FFR ≤ 0.8) from non-significant stenosis (FFR > 0.8). Statistical analysis included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy., Results: The AI model demonstrated high sensitivity, with 91.2% for any CAD and 100% for significant CAD, and high NPV, with 92.7% for any CAD and 100% for significant CAD. The diagnostic accuracy was 73.4% for any CAD and 90.4% for significant CAD. However, the PPV was lower, particularly for significant CAD (25.0%), indicating a higher incidence of false positives., Conclusion: AI-enhanced CCTA is a valuable non-invasive tool for detecting CAD in asymptomatic, low-risk populations. The AI model exhibited high sensitivity and NPV, particularly for identifying significant stenosis, reinforcing its potential role in screening. However, limitations such as a lower PPV and overestimation of disease indicate that further refinement of AI algorithms is needed to improve specificity. Despite these challenges, AI-based CCTA offers significant promise when integrated with clinical expertise, enhancing diagnostic accuracy and guiding patient management in low-risk groups., (© 2024. The Author(s).)

A better understanding of the cellular and molecular mechanisms that are involved in skeletal muscle adaptation to exercise is fundamentally important to take full advantage of the enormous benefits that exercise training offers in disease prevention and therapy. The aim of this study was to elucidate the transcriptional signatures that distinguish the endurance-trained and untrained muscles in young adult males (24 ± 3.5 years). We characterized baseline differences as well as acute exercise-induced transcriptome responses in vastus lateralis biopsy specimens of endurance-trained athletes (ET; n = 8; VO 2 max, 67.2 ± 8.9 mL/min/kg) and sedentary healthy volunteers (SED; n = 8; VO 2 max, 40.3 ± 7.6 mL/min/kg) using microarray technology. A second cohort of SED volunteers (SED-T; n = 10) followed an 8-week endurance training program to assess expression changes of selected marker genes in the course of skeletal muscle adaptation. We deciphered differential baseline signatures that reflected major differences in the oxidative and metabolic capacity of the endurance-trained and untrained muscles. SED-T individuals in the training group displayed an up-regulation of nodal regulators of oxidative adaptation after 3 weeks of training and a significant shift toward the ET signature after 8 weeks. Transcriptome changes provoked by 1 h of intense cycling exercise only poorly overlapped with the genes that constituted the differential baseline signature of ETs and SEDs. Overall, acute exercise-induced transcriptional responses were connected to pathways of contractile, oxidative, and inflammatory stress and revealed a complex and highly regulated framework of interwoven signaling cascades to cope with exercise-provoked homeostatic challenges. While temporal transcriptional programs that were activated in SEDs and ETs were quite similar, the quantitative divergence in the acute response transcriptomes implicated divergent kinetics of gene induction and repression following an acute bout of exercise. Together, our results provide an extensive examination of the transcriptional framework that underlies skeletal muscle plasticity.

Background: Physical exercise exerts a positive effect on many chronic conditions, specifically lifestyle-related diseases such as overweight and obesity, type 2 diabetes mellitus (T2DM), cardiovascular conditions and osteoarthritis (OA). As a result of common risk factors, most of these patients present with multiple conditions. Exercise- and disease-related biomarkers, such as adipokines, are emerging tools in training supervision and regulation; however, their significance in subjects with multimorbidities is unknown., Subjects and Methods: To address this issue, adipokines leptin, adiponectin and resistin were assessed in a cohort of subjects with multimorbidities (n = 39) presenting with at least two of the abovementioned conditions or relevant risk factors before and after a six-month exercise and lifestyle intervention program ('MultiPill-Exercise'), and correlated with training adaptation, namely changes in relative maximum oxygen uptake (V·O2max)., Results: There was a significant negative correlation between baseline leptin concentrations and training effect for relative V·O2max (after three months: rho = -0.54, p = 0.020 *; after six months: rho = -0.45, p = 0.013 *), with baseline leptin explaining 35% of the variance in delta relative V·O2max after three months and 23% after six months., Conclusions: Leptin might be a suitable surrogate biomarker in the context of exercise-based lifestyle intervention programs in subjects with multimorbidity.

microRNAs (miRs) have been proposed as a promising new class of biomarkers in the context of training adaptation. Using microarray analysis, we studied skeletal muscle miR patterns in sedentary young healthy females ( n = 6) before and after a single submaximal bout of endurance exercise ('reference training'). Subsequently, participants were subjected to a structured training program, consisting of six weeks of moderate-intensity continuous endurance training (MICT) and six weeks of high-intensity interval training (HIIT) in randomized order. In vastus lateralis muscle, we found significant downregulation of myomiRs, specifically miR-1, 133a-3p, and -5p, -133b, and -499a-5p. Similarly, exercise-associated miRs-23a-3p, -378a-5p, -128-3p, -21-5p, -107, -27a-3p, -126-3p, and -152-3p were significantly downregulated, whereas miR-23a-5p was upregulated. Furthermore, in an untargeted approach for differential expression in response to acute exercise, we identified n = 35 miRs that were downregulated and n = 20 miRs that were upregulated by factor 4.5 or more. Remarkably, KEGG pathway analysis indicated central involvement of this set of miRs in fatty acid metabolism. To reproduce these data in a larger cohort of all-female subjects ( n = 29), qPCR analysis was carried out on n = 15 miRs selected from the microarray, which confirmed their differential expression. Furthermore, the acute response, i.e., the difference between miR concentrations before and after the reference training, was correlated with changes in maximum oxygen uptake (V̇O 2 max) in response to the training program. Here, we found that miRs-199a-3p and -19b-3p might be suitable acute-response candidates that correlate with individual degrees of training adaptation in females.

Physical exercise has been shown to be effective in the treatment of non-communicable chronic diseases. However, patients with multiple chronic diseases (multimorbidity) have received little attention in health policy. This pilot trial served as a proof of concept of a 6-months person-oriented exercise intervention for people at risk of or with diagnosed cardiovascular diseases, diabetes mellitus type 2, overweight and/or hip/knee osteoarthritis, regarding effects on health outcomes as well as adherence and safety. The intervention (‘MultiPill-Exercise’) was designed to promote physical exercise participation, considering an individual perspective by addressing personal and environmental factors. Outcomes were assessed at baseline (t0) and after three- (t3) and six-months (t6). The primary outcome was self-reported physical exercise participation in minutes/week comparing t3 and t6 vs. t0. Secondary outcomes included cardio-respiratory fitness (maximum oxygen uptake VO2peak during incremental cycling ergometry), isometric peak torque of knee extensors and flexors, health-related quality of life (Veterans Rand 12 with its subscales of perceived general health (GH), mental health (MCS), and physical health (PCS)) and blood levels. Adherence to exercise (% of attended sessions during the first 12-weeks of the intervention) and adverse events were monitored as well. Data were analyzed using a non-parametric procedure for longitudinal data, estimating rank means (MRank) and relative treatment effects (RTE) as well as linear-mixed effect models for parametric data. The primary endpoint of physical exercise participation was significantly higher at t3 and t6 compared to baseline (t3 vs. t0: MRank = 77.1, p < 0.001, RTE: 0.66; t6 vs. t0: MRank = 70.6, p < 0.001, RTE = 0.60). Improvements at both follow-up time points compared to t0 were also found for relative VO2peak (t3 vs. t0 = 2.6 mL/kg/min, p < 0.001; t6 vs. t0 = 2.0 mL/kg/min, p = 0.001), strength of knee extensors (t3 vs. t0 = 11.7 Nm, p = 0.007; t6 vs. t0= 18.1 Nm, p < 0.001) and GH (t3 vs. t0 = 16.2, p = 0.003; t6 vs. t0 = 13.4, p = 0.008). No changes were found for MCS, PCS and for blood levels. Overall exercise adherence was 77%. No serious adverse events were recorded. Results of this pilot trial represent a first proof of concept for the intervention ‘MultiPill-Exercise’ that will now be implemented and evaluated in a real-world health care setting.

Small, non-coding RNAs (microRNAs) have been shown to regulate gene expression in response to exercise in various tissues and organs, thus possibly coordinating their adaptive response. Thus, it is likely that differential microRNA expression might be one of the factors that are responsible for different training responses of different individuals. Consequently, determining microRNA patterns might be a promising approach toward the development of individualized training strategies. However, little is known on (1) microRNA patterns and their regulation by different exercise regimens and (2) possible correlations between these patterns and individual training adaptation. Here, we present microarray data on skeletal muscle microRNA patterns in six young, female subjects before and after six weeks of either moderate-intensity continuous or high-intensity interval training on a bicycle ergometer. Our data show that n = 36 different microRNA species were regulated more than twofold in this cohort (n = 28 upregulated and n = 8 downregulated). In addition, we correlated baseline microRNA patterns with individual changes in VO 2 max and identified some specific microRNAs that might be promising candidates for further testing and evaluation in the future, which might eventually lead to the establishment of microRNA marker panels that will allow individual recommendations for specific exercise regimens., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objective: It is unclear whether and to what extent COVID-19 infection poses health risks and a chronic impairment of performance in athletes. Identification of individual health risk is an important decision-making basis for managing the pandemic risk of infection with SARS-CoV-2 in sports and return to play (RTP). Methods: This study aims 1) to analyze the longitudinal rate of seroprevalence of SARS-CoV-2 in German athletes, 2) to assess health-related consequences in athletes infected with SARS-CoV-2, and 3) to reveal effects of the COVID-19 pandemic in general and of a cleared SARS-CoV-2 infection on exercise performance. CoSmo-S is a prospective observational multicenter study establishing two cohorts: 1) athletes diagnosed positive for COVID-19 (cohort 1) and 2) federal squad athletes who perform their annual sports medical preparticipation screening (cohort 2). Comprehensive diagnostics including physical examination, laboratory blood analyses and blood biobanking, resting and exercise electrocardiogram (ECG), echocardiography, spirometry and exercise testing added by questionnaires are conducted at baseline and follow-up. Results and Conclusion: We expect that the results obtained, will allow us to formulate recommendations regarding RTP on a more evidence-based level., Competing Interests: 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., (Copyright © 2022 Niess, Widmann, Gaidai, Gölz, Schubert, Castillo, Sachs, Bizjak, Vollrath, Wimbauer, Vogel, Keller, Burgstahler, Quermann, Kerling, Schneider, Zacher, Diebold, Grummt, Beckendorf, Buitenhuis, Egger, Venhorst, Morath, Barsch, Mellwig, Oesterschlink, Wüstenfeld, Predel, Deibert, Friedmann-Bette, Mayer, Hirschmüller, Halle, Steinacker, Wolfarth, Meyer, Böttinger, Flechtner-Mors, Bloch, Haller, Roecker and Reinsberger.)

Objectives: To evaluate computed tomography fractional flow reserve (FFR CT ) values in distal parts of the coronaries in an asymptomatic cohort of marathon runners without any coronary stenosis for potentially false-positive values., Methods: Ninety-eight asymptomatic male marathon runners (age 53 ± 7 years) were enrolled in a prospective monocentric study and underwent coronary computed tomography angiography (CCTA). CCTA data were analyzed for visual coronary artery stenosis. FFR CT was evaluated in 59 participants without coronary artery stenosis in proximal, mid, and distal coronary sections using an on-site software prototype., Results: In participants without coronary artery stenosis, abnormal FFR CT values ≤ 0.8 in distal segments were found in 22 participants (37%); in 19 participants in the LAD; in 5 participants in the LCX; and in 4 participants in the RCA. Vessel diameters in participants with FFR CT values > 0.80 compared to ≤ 0.80 were 1.6 ± 0.3 mm versus 1.5 ± 0.3 mm for distal LAD (p = 0.025), 1.8 ± 0.3 mm versus 1.6 ± 0.5 mm for distal LCX (p = 0.183), and 2.0 ± 0.4 mm versus 1.5 ± 0.2 mm for distal RCA (p < 0.001)., Conclusions: Abnormal FFR CT values of ≤ 0.8 frequently occurred in distal coronary segments in subjects without any anatomical coronary artery stenosis. This effect is only to some degree explainable by small distal vessel diameters. Therefore, the validity of hemodynamic relevance evaluation using FFR CT in distal coronary artery segment stenosis is reduced., Key Points: • Abnormal FFR CT values (≤ 0.8) occurred in over a third of the subjects in the distal LAD despite the absence of coronary artery stenosis.. • Therefore, the validity of hemodynamic relevance evaluation in distal coronary artery segment stenosis is reduced. • Decision-making based on abnormal FFR CT values in distal vessel sections should be performed with caution and only in combination with visual assessment of the grade of stenosis.., (© 2021. The Author(s).)

The evaluation of the maximal oxygen uptake ( V ˙ O 2 max ) following exercise training is the classical assessment of training effectiveness. Research has lacked in investigating whether individuals that do not respond to the training intervention ( V ˙ O 2 max ), also do not improve in other health-related parameters. We aimed to investigate the cardiovascular and metabolic adaptations (i.e., performance, body composition, blood pressure, vascular function, fasting blood markers, and resting cardiac function and morphology) to exercise training among participants who showed different levels of V ˙ O 2 max responsiveness. Healthy sedentary participants engaged in a 6-week exercise training program, three times a week. Our results showed that responders had a greater increase in peak power output, second lactate threshold, and microvascular responsiveness, whereas non-responders had a greater increase in cycling efficiency. No statistical differences were observed in body composition, blood pressure, fasting blood parameters, and resting cardiac adaptations. In conclusion, our study showed, for the first time, that in addition to the differences in the V ˙ O 2 max , a greater increase in microvascular responsiveness in responders compared to non-responders was observed. Additionally, responders and non-responders did not show differences in the adaptations on metabolic parameters. There is an increasing need for personalized training prescription, depending on the target clinical outcome., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Breath-hold diving involves environmental challenges, such as water immersion, hydrostatic pressure, and asphyxia, that put the respiratory system under stress. While training and inherent individual factors may increase tolerance to these challenges, the limits of human respiratory physiology will be reached quickly during deep breath-hold dives. Nonetheless, world records in deep breath-hold diving of more than 214 m of seawater have considerably exceeded predictions from human physiology. Investigations of elite breath-hold divers and their achievements revised our understanding of possible physiological adaptations in humans and revealed techniques such as glossopharyngeal breathing as being essential to achieve extremes in breath-hold diving performance. These techniques allow elite athletes to increase total lung capacity and minimize residual volume, thereby reducing thoracic squeeze. However, the inability of human lungs to collapse early during descent enables respiratory gas exchange to continue at greater depths, forcing nitrogen (N 2 ) out of the alveolar space to dissolve in body tissues. This will increase risk of N 2 narcosis and decompression stress. Clinical cases of stroke-like syndromes after single deep breath-hold dives point to possible mechanisms of decompression stress, caused by N 2 entering the vasculature upon ascent from these deep dives. Mechanisms of neurological injury and inert gas narcosis during deep breath-hold dives are still incompletely understood. This review addresses possible hypotheses and elucidates factors that may contribute to pathophysiology of deep freediving accidents. Awareness of the unique challenges to pulmonary physiology at depth is paramount to assess medical risks of deep breath-hold diving., Competing Interests: 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., (Copyright © 2021 Tetzlaff, Lemaitre, Burgstahler, Luetkens and Eichhorn.)

Purpose: We investigated the cardiovascular individual response to 6 weeks (3×/week) of work-matched within the severe-intensity domain (high-intensity interval training, HIIT) or moderate-intensity domain (moderate-intensity continuous training, MICT). In addition, we analyzed the cardiovascular factors at baseline underlying the response variability., Methods: 42 healthy sedentary participants were randomly assigned to HIIT or MICT. We applied the region of practical equivalence-method for identifying the levels of responders to the maximal oxygen uptake (V̇O 2max ) response. For investigating the influence of cardiovascular markers, we trained a Bayesian machine learning model on cardiovascular markers., Results: Despite that HIIT and MICT induced significant increases in V̇O 2max , HIIT had greater improvements than MICT (p < 0.001). Greater variability was observed in MICT, with approximately 50% classified as "non-responder" and "undecided". 20 "responders", one "undecided" and no "non-responders" were observed in HIIT. The variability in the ∆V̇O 2max was associated with initial cardiorespiratory fitness, arterial stiffness, and left-ventricular (LV) mass and LV end-diastolic diameter in HIIT; whereas, microvascular responsiveness and right-ventricular (RV) excursion velocity showed a significant association in MICT., Conclusion: Our findings highlight the critical influence of exercise-intensity domains and biological variability on the individual V̇O 2max response. The incidence of "non-responders" in MICT was one third of the group; whereas, no "non-responders" were observed in HIIT. The incidence of "responders" was 11 out of 21 participants in MICT, and 20 out of 21 participants in HIIT. The response in HIIT showed associations with baseline fitness, arterial stiffness, and LV-morphology; whereas, it was associated with RV systolic function in MICT.