Category Archives: Publications

Heart failure with preserved ejection fraction: relevance of a dedicated dyspnoea clinic.

Verwerft J; Soens L; Wynants J; Meysman M; Jogani S; Plein D; Stroobants S; Herbots L; Verbrugge FH;

European heart journal [Eur Heart J] 2023 Mar 16.
Date of Electronic Publication: 2023 Mar 16.

Background and Aims: Heart failure with preserved ejection fraction (HFpEF) is a syndrome with a heterogeneous presentation. This study provides an in-depth description of haemodynamic and metabolic alterations revealed by systematic assessment through cardiopulmonary exercise testing combined with exercise echocardiography (CPETecho) within a dedicated dyspnoea clinic.
Methods and Results: Consecutive patients (n = 297), referred to a dedicated dyspnoea clinic using a standardized workup including CPETecho, with HFpEF diagnosed through a H2FPEF score ≥6 or HFA-PEFF score ≥5, were evaluated. A median of four haemodynamic/metabolic alterations was uncovered per patient: impaired stroke volume reserve (73%), impaired chronotropic reserve (72%), exercise pulmonary hypertension (65%), and impaired diastolic reserve (64%) were the most frequent cardiac alterations. Impaired peripheral oxygen extraction and a ventilatory limitation were present in 40% and 39%, respectively. In 267 patients (90%), 575 further diagnostic examinations were recommended (median of two tests per patient). Cardiac magnetic resonance imaging, coronary or amyloidosis workup, ventilation-perfusion scanning, and pulmonology referral were each recommended in approximately one out of three patients. In 293 patients (99%), 929 cardiovascular drug optimizations were performed (median of 3 modifications per patient). In 110 patients (37%), 132 cardiovascular interventions were performed, with ablation as the most frequent procedure.
Conclusion: Holistic workup of HFpEF patients within a multidisciplinary, dedicated dyspnoea clinic, including systematic implementation of CPETecho reveals various haemodynamic/metabolic alterations, leading to further diagnostic testing and potential treatment changes in the majority of cases.

The impact of anti-eosinophilic therapy on exercise capacity and inspiratory muscle strength in patients with severe asthma.

Franceschi E; Drick N; Fuge J; Santus P; Fischer B; Kayser M; Welte T; Suhling H;

ERJ open research [ERJ Open Res] 2023 Mar 20; Vol. 9 (2).
Date of Electronic Publication: 2023 Mar 20 (Print Publication: 2023).

Introduction: Exercise limitation is frequently described among asthmatic patients and could be related to different mechanisms of the pulmonary, cardiovascular and muscular systems. Despite this, cardiopulmonary exercise testing (CPET) does not have an established role in the management of severe asthma. The aim of our study was to investigate the role of CPET and inspiratory pressure measurement in exercise capacity and muscle strength in severe asthmatic patients treated with anti-IL-5 therapy.
Methods: A monocentric observational study was conducted at Hanover Medical School, Germany, from April 2018 to June 2019. Patients affected by severe asthma treated with either mepolizumab or benralizumab were included. All patients underwent CPET before the initiation of antibody therapy and after 3 months, and follow-up visits were scheduled at 3, 6 and 12 months with plethysmography, inspiratory pressure measurement and blood gas analysis.
Results: 14 patients were enrolled: 10 (71.4%) females, median age 52 years (IQR 47-61). Seven patients were treated with benralizumab, seven with mepolizumab. Oxygen uptake ( VO 2 peak) did not change significantly after 3 months of antibody treatment, while the mean value of the breathing reserve exhaustion reduced significantly from 78% to 60% (p=0.004). Whereas at baseline seven patients depleted the breathing reserve and two of them experienced oxygen desaturation during exercise, at 3 months no one presented any desaturation or breathing reserve exhaustion. The inspiratory pressure remained unchanged before and after the antibody therapy.
Conclusion: CPET could show hints of alveolar recruitment and ventilatory efficiency in severe asthma patients treated with antibody therapy.

Association Between Aortic Stiffness and Exercise Tolerance in Patients at the Risk Stage of Heart Failure.

Mizoguchi T; Sugiura T; Kawada Y; Yamamoto J; Yokoi M; Nakasuka K; DMori K; Kikuchi S; Ito T;Kitada S; Goto T; Seo Y

Circulation journal : official journal of the Japanese Circulation Society [Circ J] 2023 Mar 21.
Date of Electronic Publication: 2023 Mar 21.

Background: The number of patients with heart failure (HF) has increased, and it is crucial to prevent the development of HF in patients at risk of HF. The present study aimed to risk stratify patients in Stage A and B HF based on associations between exercise-induced changes in aortic stiffness and exercise tolerance.Methods and Results: Patients in Stage A and B HF who performed a cardiopulmonary exercise test were enrolled in the study (n=106; median age 65.0 years [interquartile range 52.8-73.0 years]). Exercise tolerance was examined by the percentage of predicted peak oxygen consumption (%V̇O 2 peak). The ascending aortic pressure waveform was estimated non-invasively. Aortic stiffness was assessed using the augmentation index (AIx) and reflection magnitude (RM). Multivariable regression analysis showed that AIx measured both before and after exercise was significantly associated with %V̇O 2 peak (β=-0.221 [P=0.049] and β=-0.342 [P=0.003], respectively). When participants were divided into %V̇O 2 peak subgroups using a cut-off value of 60%, RM decreased immediately after exercise and remained lower 5 min after exercise in the group with preserved exercise tolerance, but recovered to baseline levels 5 min after exercise in the group with reduced exercise tolerance.
Conclusions: Exercise-induced increases in aortic stiffness were associated with exercise tolerance in patients at risk of HF, suggesting that exercise-induced changes in aortic stiffness may be useful to stratify high-risk patients.

Athlete’s heart or heart disease in the athlete? Evaluation by cardiopulmonary exercise testing.

Segreti A; Picarelli F; DI Gioia G; Coletti F; Crispino SP; Fanale V; Fossati C; Antonelli Incalzi R; Pigozzi F; Grigioni F

The Journal of sports medicine and physical fitness [J Sports Med Phys Fitness] 2023 Mar 23.
Date of Electronic Publication: 2023 Mar 23.

Routine or vigorous training, particularly in competitive and elite athletes practicing dynamic sports, leads to a constellation of structural and functional cardiovascular adaptations, facilitating an increased capacity to deliver oxygen to the working muscles during sustained physical exertion. Cardiopulmonary exercise testing is the most accurate and objective method to assess performance in athletes. Although still underutilized, it provides a window into the unique cardiovascular response to exercise in athletes, integrating parameters obtained by the traditional exercise test with breath-by-breath analysis of oxygen consumption, carbon dioxide production, ventilation, and other derived parameters. This review aimed to describe the several applications of cardiopulmonary exercise testing in athletes with a principal focus on the ability to identify cardiovascular adaptations and differentiate an athlete’s heart from early cardiomyopathy. In this context, cardiopulmonary exercise testing provides many applications involving exercise physiology in athletes, allowing a precise evaluation of cardiovascular efficiency, the entity of the adaptations, the response to a training program, and identifying early modifications that could reveal early cardiomyopathy. Therefore, thanks to its several applications, this pivotal test allows us to obtain essential information about the athlete’s physiology and differentiate between the expected response of a trained athlete from early cardiomyopathy.

Do cardiopulmonary exercise tests predict summit success and acute mountain sickness? A prospective observational field study at extreme altitude.

Seiler T; Nakas CT; Brill AK; Hefti U; Hilty MP; DPerret-Hoigné E; Sailer J; Kabitz HJ; Merz TM; Pichler Hefti J;

British journal of sports medicine [Br J Sports Med] 2023 Mar 10.
Date of Electronic Publication: 2023 Mar 10.

Objective: During a high-altitude expedition, the association of cardiopulmonary exercise testing (CPET) parameters with the risk of developing acute mountain sickness (AMS) and the chance of reaching the summit were investigated.
Methods: Thirty-nine subjects underwent maximal CPET at lowlands and during ascent to Mount Himlung Himal (7126 m) at 4844 m, before and after 12 days of acclimatisation, and at 6022 m. Daily records of Lake-Louise-Score (LLS) determined AMS. Participants were categorised as AMS+ if moderate to severe AMS occurred.
Results: Maximal oxygen uptake (V̇O 2max ) decreased by 40.5%±13.7% at 6022 m and improved after acclimatisation (all p<0.001). Ventilation at maximal exercise (VE max ) was reduced at 6022 m, but higher VE max was related to summit success (p=0.031). In the 23 AMS+ subjects (mean LLS 7.4±2.4), a pronounced exercise-induced oxygen desaturation (ΔSpO 2exercise ) was found after arrival at 4844 m (p=0.005). ΔSpO 2exercise >-14.0% identified 74% of participants correctly with a sensitivity of 70% and specificity of 81% for predicting moderate to severe AMS. All 15 summiteers showed higher V̇O 2max (p<0.001), and a higher risk of AMS in non-summiteers was suggested but did not reach statistical significance (OR: 3.64 (95% CI: 0.78 to 17.58), p=0.057). V̇O 2max ≥49.0 mL/min/kg at lowlands and ≥35.0 mL/min/kg at 4844 m predicted summit success with a sensitivity of 46.7% and 53.3%, and specificity of 83.3% and 91.3%, respectively.
Conclusion: Summiteers were able to sustain higher VE max throughout the expedition. Baseline V̇O 2max below 49.0 mL/min/kg was associated with a high chance of 83.3% for summit failure, when climbing without supplemental oxygen. A pronounced drop of SpO 2exercise at 4844 m may identify climbers at higher risk of AMS.

Assessing cardiorespiratory fitness relative to sex improves surgical risk stratification.

Rose GA; Davies RG; Torkington J; Berg RMG; Appadurai IR; Poole DC; Bailey DM;

European journal of clinical investigation [Eur J Clin Invest] 2023 Mar 13, pp. e13981.
Date of Electronic Publication: 2023 Mar 13.

Background: To what extent sex-related differences in cardiorespiratory fitness (CRF) impact postoperative patient mortality and corresponding implications for surgical risk stratification remains to be established.
Methods: To examine this, we recruited 640 patients (366 males vs. 274 females) who underwent cardiopulmonary exercise testing prior to elective colorectal surgery. Patients were defined high risk if peak oxygen uptake was <14.3 mL kg -1 min -1 and ventilatory equivalent for carbon dioxide at ‘anaerobic threshold’ >34. Between-sex CRF and mortality was assessed, and sex-specific CRF thresholds predictive of mortality calculated.
Results: Seventeen percent of deaths were attributed to sub-threshold CRF, which was higher than established risk factors for cardiovascular disease (CVD). The group (independent of sex) exhibited a 5-fold higher mortality (high vs. low risk patients hazard ratio =4.80, 95% confidence interval 2.73 to 8.45, P <0.001). Females exhibited 39% lower CRF (P <0.001) with more classified high risk than males (36 vs. 23%, P=0.001), yet mortality was not different (P =0.544). Upon reformulation of sex-specific CRF thresholds, lower cut-offs for mortality were observed in females, and consequently, fewer (20%) were stratified with sub-threshold CRF compared to the original 36% (P<0.001).
Conclusions: Low CRF accounted for more deaths than traditional CVD risk factors and when CRF was considered relative to sex, the disproportionate number of females stratified unfit was corrected. These findings support clinical consideration of ‘sex-specific’ CRF thresholds to better inform postoperative mortality and improve surgical risk stratification.

Influence of different data-averaging methods on mean values of selected variables derived from preoperative cardiopulmonary exercise testing in patients scheduled for colorectal surgery

 Franssen , RFW; Sanders, BHE; Takken, T;  Vogelaar, FJ;  Janssen-Heijnen, MLG;  Bongers, BC;
Published: March 16, 2023

Introduction: Patients with a low cardiorespiratory fitness (CRF) undergoing colorectal cancer surgery have a high risk for postoperative complications. Cardiopulmonary exercise testing (CPET) to assess CRF is the gold standard for preoperative risk assessment. To aid interpretation of raw breath-by-breath data, different methods of data-averaging can be applied. This study aimed to investigate the influence of different data-averaging intervals on CPET variables used for preoperative risk assessment, as well as to evaluate whether different data-averaging intervals influence preoperative risk assessment

Methods: A total of 21 preoperative CPETs were interpreted by two exercise physiologists using stationary time-based data-averaging intervals of 10, 20, and 30 seconds and rolling average intervals of 3 and 7 breaths. Mean values of CPET variables between different data averaging intervals were compared using repeated measures ANOVA. The variables of interest were oxygen uptake at peak exercise (VO2peak), oxygen uptake at the ventilatory anaerobic threshold (VO2VAT), oxygen uptake efficiency slope (OUES), the ventilatory equivalent for carbon dioxide at the ventilatory anaerobic threshold (VE/VCO2VAT), and the slope of the relationship between the minute ventilation and carbon dioxide production (VE/VCO2-slope)

Results: Between data-averaging intervals, no statistically significant differences were found in the mean values of CPET variables except for the ventilatory equivalent for carbon dioxide at the ventilatory anaerobic threshold (P = 0.001). No statistically significant differences were found in the proportion of patients classified as high or low risk regardless of the used data-averaging interval.

Conclusion: There appears to be no significant or clinically relevant influence of the evaluated data-averaging intervals on the mean values of CPET outcomes used for preoperative risk assessment. Clinicians may choose a data-averaging interval that is appropriate for optimal interpretation and data visualization of the preoperative CPET. Nevertheless, caution should be taken as the chosen data-averaging interval might lead to substantial within-patient variation for individual patients.

Stable fitness during COVID-19: Results of serial testing in a cohort of youth with heart disease.

Powell AW; Mays WA; Wittekind SG; Chin C; Knecht SK; Lang SM; Opotowsky AR;

Frontiers in pediatrics [Front Pediatr] 2023 Feb 20; Vol. 11, pp. 1088972.
Date of Electronic Publication: 2023 Feb 20 (Print Publication: 2023).

Background: Little is known about how sport and school restrictions early during the novel coronavirus 2019 (COVID-19) pandemic impacted exercise performance and body composition in youth with heart disease (HD).
Methods: A retrospective chart review was performed on all patients with HD who had serial exercise testing and body composition via bioimpedance analysis performed within 12 months before and during the COVID-19 pandemic. Formal activity restriction was noted as present or absent. Analysis was performed with a paired t -test.
Results: There were 33 patients (mean age 15.3 ± 3.4 years; 46% male) with serial testing completed (18 electrophysiologic diagnosis, 15 congenital HD). There was an increase in skeletal muscle mass (SMM) (24.1 ± 9.2-25.9 ± 9.1 kg, p  < 0.0001), weight (58.7 ± 21.5-63.9 ± 22 kg, p  < 0.0001), and body fat percentage (22.7 ± 9.4-24.7 ± 10.4%, p  = 0.04). The results were similar when stratified by age <18 years old ( n  = 27) or by sex (male 16, female 17), consistent with typical pubertal changes in this predominantly adolescent population. Absolute peak VO 2 increased, but this was due to somatic growth and aging as evidenced by no change in % of predicted peak VO 2 . There remained no difference in predicted peak VO 2 when excluding patients with pre-existing activity restrictions ( n  = 12). Review of similar serial testing in 65 patients in the 3 years before the pandemic demonstrated equivalent findings.
Conclusions: The COVID-19 pandemic and related lifestyle changes do not appear to have had substantial negative impacts on aerobic fitness or body composition in children and young adults with HD.

Prognostic Significance of Peak Workload-to-Weight Ratio by Cardiopulmonary Exercise Testing in Chronic Heart Failure.

Yasui Y; Nakamura K; Omote K; Ishizaka S; Takenaka S; Mizuguchi Y; Shimono Y; Kazui S; Takahashi Y; Saiin K; Naito S; Tada A; Kobayashi Y; Sato T; Kamiya K; Nagai T; Anzai T;

The American journal of cardiology [Am J Cardiol] 2023 Mar 01; Vol. 193, pp. 37-43.
Date of Electronic Publication: 2023 Mar 01.

The prognostic impact of peak workload-to-weight ratio (PWR) during cardiopulmonary exercise testing (CPET) and its determinants in patients with chronic heart failure (CHF) are not well understood. Consecutive 514 patients with CHF referred for CPET at the Hokkaido University Hospital between 2013 and 2018 were identified. The primary outcome was a composite of hospitalization because of worsening heart failure and death. PWR was calculated as peak workload normalized to body weight (W/kg) by CPET. Patients with low PWR (cut-off median 1.38 [W/kg], n = 257) were older and more anemic than those with high PWR (n = 257). In CPET, patients with low PWR displayed reduced peak oxygen consumption and impaired ventilatory efficiency compared with those with high PWR, whereas the peak respiratory exchange ratio was not significantly different between the 2 groups. There were 89 patients with events over a median follow-up period of 3.3 (interquartile range 0.8 to 5.5) years. The incidence of composite events was significantly higher in patients with low PWR than in those with high PWR (log-rank p <0.0001). In the multivariable Cox regression, lower PWR was associated with adverse events (hazard ratio 0.31, 95% confidence interval 0.13 to 0.73, p = 0.008). Low hemoglobin concentration was strongly related to impaired PWR (β coefficient = 0.43, per 1 g/100 ml increased, p <0.0001). In conclusion, PWR was associated with worse clinical outcomes, where blood hemoglobin was strongly related to PWR. Further study is required to identify therapies targeting peak workload achievements in exercise stress tests to improve the outcome in patients with CHF.