Pietrzak R; Książczyk TM; Franke M; Werner B;

Scientific reports [Sci Rep] 2023 Apr 11; Vol. 13 (1), pp. 5897.
Date of Electronic Publication: 2023 Apr 11.

Premature ventricular contractions (PVC) are frequently seen in children. We evaluated left ventricular diastolic function in PVC children with normal left ventricular systolic function to detect whether diastolic function disturbances affect physical performance. The study group consisted of 36 PVC children, and the control group comprised 33 healthy volunteers. Echocardiographic diastolic function parameters such as left atrial volume index (LAVI), left atrial strains (AC-R, AC-CT, AC-CD), E wave, E deceleration time (Edt), E/E’ ratio, and isovolumic relaxation time (IVRT) were measured. In the cardiopulmonary exercise test (CPET), oxygen uptake (VO _{2 max} ) was registered. Evaluation of diastolic function parameters revealed statically significant differences between the patients and controls regarding Edt (176.58 ± 54.8 ms vs. 136.94 ± 27.8 ms, p < 0.01), E/E’ (12.6 ± 3.0 vs. 6.7 ± 1.0, p < 0.01), and IVRT (96.6 ± 19.09 ms. vs. 72.86 ± 13.67 ms, p < 0.01). Left atrial function was impaired in the study group compared to controls: LAVI (25.3 ± 8.2 ml/m ² vs. 19.2 ± 7.5 ml/m ² , p < 0.01), AC-CT (34.8 ± 8.6% vs. 44.8 ± 11.8%, p < 0.01), and AC-R-(6.0 ± 4.9% vs. -11.5 ± 3.5%, p < 0.01), respectively. VO2 max in the study group reached 33.1 ± 6.2 ml/min/kg. A statistically significant, moderate, negative correlation between VO2 max and E/E’ (r = -0.33, p = 0.02) was found. Left ventricular diastolic function is impaired and deteriorates with the arrhythmia burden increase in PVC children. Ventricular arrhythmia in young individuals may be related to the filling pressure elevation and drive to exercise capacity deterioration.

Laukkanen J; Isiozor NM; Willeit P; Kunutsor SK;

Cardiology [Cardiology] 2023 Apr 13.
Date of Electronic Publication: 2023 Apr 13.

Introduction: Haemodynamic gain index (HGI) is a novel haemodynamic parameter which can be obtained from cardiopulmonary exercise testing (CPX), but its association with sudden cardiac death (SCD) is not known. We aimed to assess the association of HGI with SCD risk in a long-term prospective cohort study.
Methods: Haemodynamic gain index was calculated using heart rate and systolic blood pressure (SBP) measured in 1897 men aged 42-61 years during CPX from rest to peak exercise, using the formula: [(Heart rate max x SBPmax) – (Heart rate rest x SBPrest)]/(Heart rate rest x SBPrest). Cardiorespiratory fitness (CRF) was measured using respiratory gas exchange analysis. Multivariable adjusted hazard ratios (HRs) (95% confidence intervals, CIs) were analyzed for SCD.
Results: During a median follow-up of 28.7 years, 205 SCDs occurred. The risk of SCD decreased gradually with increasing HGI (p-value for non-linearity=.63). A unit (bpm/mmHg) higher HGI was associated with a decreased risk of SCD (HR 0.84; 95% CI 0.71-0.99), which was attenuated following adjustment for CRF. Cardiorespiratory fitness was inversely associated with SCD, which remained after further adjustment for HGI: (HR 0.85; 95% CI 0.77-0.94) per each unit higher CRF. Addition of HGI to a SCD risk prediction model containing established risk factors improved risk discrimination (C-index change=0.0096; p=.017) and reclassification (NRI=39.40%, p=.001). The corresponding values for CRF were (C-index change=0.0178; p=.007) and (NRI=43.79%, p=.001).
Conclusion: Higher HGI during CPX is associated with a lower SCD risk, consistent with a dose-response relationship, but dependent on CRF levels. Though HGI significantly improves the prediction and classification of SCD beyond common cardiovascular risk factors, CRF remains a stronger risk indicator and predictor of SCD compared to HGI.

Orlandi R; Rinaldo RF; Mazzucco A; Baccelli A; Mondoni M; Marchetti F; Zagaria M; Cefalo J; Leporati A;
Montoli M;Ghilardi G; Baisi A; Centanni S;

Frontiers in surgery [Front Surg] 2023 Mar 16; Vol. 10, pp. 1130919.
Date of Electronic Publication: 2023 Mar 16 (Print Publication: 2023).

Objective: Cardiopulmonary exercise testing (CPET) is currently recommended for all patients undergoing lung resection with either respiratory comorbidities or functional limitations. The main parameter evaluated is oxygen consumption at peak (VO ₂ peak). Patients with VO ₂ peak above 20 ml/kg/min are classified as low risk surgical candidates. The aims of this study were to evaluate postoperative outcomes of low-risk patients, and to compare their outcomes with those of patients without pulmonary impairment at respiratory function testing.
Methods: Retrospective monocentric observational study was designed, evaluating outcomes of patients undergoing lung resection at San Paolo University Hospital, Milan, Italy, between January 2016 and November 2021, preoperatively assessed by CPET, according to 2009 ERS/ESTS guidelines. All low-risk patients undergoing any extent surgical lung resection for pulmonary nodules were enrolled. Postoperative major cardiopulmonary complications or death, occurring within 30 days from surgery, were assessed. A case-control study was nested, matching 1:1 for type of surgery the cohort population with control patients without functional respiratory impairment consecutively undergoing surgery at the same centre in the study period.
Results: A total of 80 patients were enrolled: 40 subjects were preoperatively assessed by CPET and deemed at low risk, whereas 40 subjects represented the control group. Among the first, 4 patients (10%) developed major cardiopulmonary complications, and 1 patient (2.5%) died within 30 days from surgery. In the control group, 2 patients (5%) developed complications and none of the patients (0%) died. The differences in morbidity and mortality rates did not reach statistically significance. Instead, age, weight, BMI, smoking history, COPD incidence, surgical approach, FEV1, Tiffenau, DLCO and length of hospital stay resulted significantly different between the two groups. At a case-by-case analysis, CPET revealed a pathological pattern in each complicated patient, in spite of VO ₂ peak above target for safe surgery.
Conclusions: Postoperative outcomes of low-risk patients undergoing lung resections are comparable to those of patients without any pulmonary functional impairment; nonetheless the formers represent a dramatically different category of individuals from the latter and may harbour few patients with worse outcomes. CPET variables overall interpretation may add to the VO ₂ peak in identifying higher risk patients, even in this subgroup.

Campos NE; Vendrusculo FM; Pérez-Ruiz M; Donadio MVF;

Respiratory care [Respir Care] 2023 Apr 04.
Date of Electronic Publication: 2023 Apr 04.

Background: Whereas pulmonary exacerbations and aerobic fitness play a key role in the prognosis of cystic fibrosis (CF), the use of ventilatory threshold data as markers of exacerbation risk has been scarcely addressed. This study sought to examine the association between aerobic fitness, assessed through ventilatory threshold variables recorded during cardiopulmonary exercise testing (CPET), and the risk of exacerbations in individuals with CF.
Methods: Participants of this retrospective cohort study were subjects from 6 y of age. Over a 4-y period, the following data were recorded: lung function indicators, CPET variables, time to first exacerbation and antibiotic use, along with demographic, clinical, and anthropometric data.
Results: The mean age of 20 subjects included was 16 ± 5.4 y. Univariate regression analysis revealed that lung function (FEV ₁ : Cox hazard ratio [HR] 0.97 , P = .03; and forced expiratory flow between 25-75% of vital capacity [FEF _25-75 ]: Cox HR 0.98 , P = .036) and aerobic fitness (oxygen consumption [V̇ _{O 2} ] at ventilatory threshold: Cox HR 0.94 , P = .01; and ventilatory equivalent for carbon dioxide [V̇ _E /V̇ _{CO 2} ] at ventilatory threshold: Cox HR 1.13 , P = .049) were associated with exacerbation risk, whereas in the multivariate model, only V̇ _{O 2} at the ventilatory threshold (%max) (Cox HR 0.92 , P = .01) had a significant impact on this risk. Consistently, individuals experiencing exacerbation had significantly lower V̇ _{O 2} values (%max) at the ventilatory threshold ( P = .050) and higher ventilatory equivalent for oxygen consumption (V̇ _E /V̇ _{O 2} ) ( P = .040) and V̇ _E /V̇ _{O 2} ( P = .037) values at the ventilatory threshold. Time to exacerbation was significantly correlated with V̇ _{O 2} at the ventilatory threshold (r = 0.50, P = .02), V̇ _E /V̇ _{O 2} (r = -0.48, P = .02), and V̇ _E /V̇ _{CO 2} (r = -0.50, P = .02).
Conclusions: Our results suggest an association between CPET variables at the ventilatory threshold and exacerbations. Percentage V̇ _{O 2} at the ventilatory threshold could serve as a complementary variable to monitor exacerbations in people with CF.

Cavalcante S; Viamonte S; Cadilha RS; Ribeiro IP; Gonçalves AC; Sousa-Venâncio J; Gouveia M; Teixeira M; Santos M; Oliveira J; Ribeiro F;

Current issues in molecular biology [Curr Issues Mol Biol] 2023 Feb 28; Vol. 45 (3), pp. 1950-1960.
Date of Electronic Publication: 2023 Feb 28.

The impact of exercise on the levels of endothelial progenitor cells (EPCs), a marker of endothelial repair and angiogenesis, and circulating endothelial cells (CECs), an indicator of endothelial damage, in heart failure patients is largely unknown. This study aims to evaluate the effects of a single exercise bout on the circulating levels of EPCs and CECs in heart failure patients. Thirteen patients with heart failure underwent a symptom-limited maximal cardiopulmonary exercise test to assess exercise capacity. Before and after exercise testing, blood samples were collected to quantify EPCs and CECs by flow cytometry. The circulating levels of both cells were also compared to the resting levels of 13 volunteers (age-matched group). The maximal exercise bout increased the levels of EPCs by 0.5% [95% Confidence Interval, 0.07 to 0.93%], from 4.2 × 10 ^-3 ± 1.5 × 10 ^-3 % to 4.7 × 10 ^-3 ± 1.8 × 10 ^-3 % ( p = 0.02). No changes were observed in the levels of CECs. At baseline, HF patients presented reduced levels of EPCs compared to the age-matched group ( p = 0.03), but the exercise bout enhanced circulating EPCs to a level comparable to the age-matched group (4.7 × 10 ^-3 ± 1.8 × 10 ^-3 % vs. 5.4 × 10 ^-3 ± 1.7 × 10 ^-3 %, respectively, p = 0.14). An acute bout of exercise improves the potential of endothelial repair and angiogenesis capacity by increasing the circulating levels of EPCs in patients with heart failure.

Ito W; Uchiyama K; Mitsuno R; Sugita E; Nakayama T; Ryuzaki T; Takahashi R; Katsumata Y; Hayashi K; Kanda T; Washida N; Sato K; IItoh H;

Frontiers in physiology [Front Physiol] 2023 Mar 07; Vol. 14, pp. 1155281.
Date of Electronic Publication: 2023 Mar 07 (Print Publication: 2023).

Objective: Diminished physical capacity is common and progressive in patients undergoing dialysis, who are also prone to deficiency in carnitine, which plays a pivotal role in maintaining skeletal muscle and cardiac function. The present study aimed to evaluate the association of carnitine profile with exercise parameters in patients with incident dialysis.
Design and Methods: This was a single-center cross-sectional study including 87 consecutive patients aged 20-90 years who were initiated on dialysis in Keio University Hospital between December 2019 and December 2022 and fulfilled the eligibility criteria. Exercise parameters were evaluated via cardiopulmonary testing (CPX) using the electronically braked STRENGTH ERGO 8 ergometer, whereas the carnitine profile was assessed by determining serum free carnitine (FC), acylcarnitine (AC) levels and AC/FC ratio.
Results: The mean cohort age was 62.1 ± 15.2 years, with male and hemodialysis predominance (70% and 73%, respectively). AC/FC was 0.46 ± 0.15, and CPX revealed peak oxygen consumption (VO ₂ ) of 13.9 ± 3.7 (mL/kg/min) with percent-predicted peak VO ₂ of 53.6% ± 14.7% and minute ventilation (VE)/carbon dioxide output (VCO ₂ ) slope of 35.1 ± 8.0. Fully-adjusted multivariate linear regression analysis showed that AC/FC was significantly associated with decreased peak VO ₂ (β, -5.43 [95% confidence interval (CI), -10.15 to -0.70]) and percent-predicted peak VO ₂ (β, -19.98 [95% CI, -38.43 to -1.52]) and with increased VE/VCO ₂ slope (β, 13.76 [95% CI, 3.78-23.75]); FC and AC did not exhibit similar associations with these parameters. Moreover, only AC/FC was associated with a decreased peak work rate (WR), percent-predicted WR, anaerobic threshold, delta VO ₂ /delta WR, and chronotropic index.
Conclusion: In patients on incident dialysis, exercise parameters, including those related to both skeletal muscle and cardiac function, were strongly associated with AC/FC, a marker of carnitine deficiency indicating altered fatty acid metabolism. Further studies are warranted to determine whether carnitine supplementation can improve exercise capacity in patients on incident dialysis.

Gentili F; Calcagni G; Cantarutti N; Manno EC; Cafiero G; Tranchita E; Salvati A; Palma P; Giordano U; Drago F; Turchetta A;

Journal of clinical medicine [J Clin Med] 2023 Mar 19; Vol. 12 (6).
Date of Electronic Publication: 2023 Mar 19.

Multisystem inflammatory syndrome in children (MIS-C) is a serious health condition that imposes a long-term follow-up. The purpose of our pilot study is to evaluate the usefulness of the cardiopulmonary stress test (CPET) in the follow-up after MIS-C. All patients admitted for MIS-C in our hospital in the 12 months preceding the date of observation were considered for inclusion in the study. Pre-existing cardio-respiratory diseases and/or the lack of collaboration were the exclusion criteria. At enrolment, each subject passed a cardiological examination, rest ECG, echocardiogram, 24 h Holter-ECG, blood tests, and a CPET complete of spirometry. A total of 20 patients met the inclusion criteria (11.76 ± 3.29 years, 13 male). In contrast to the normality of all second-level investigations, CPET showed lower-than-expected peakVO ₂ and peak-oxygen-pulse values (50% of cases) and higher-than-expected VE/VCO _2- slope values (95% of cases). A statistically significant inverse correlation was observed between P-reactive-protein values at admission and peakVO ₂ /kg values ( p = 0.034), uric acid values at admission, and peakVO ₂ ( p = 0.011) or peak-oxygen-pulse expressed as a percentage of predicted ( p = 0.021), NT-proBNP values at admission and peakVO ₂ expressed as a percentage of predicted ( p = 0.046). After MIS-C (4-12 months) relevant anomalies can be observed at CPET, which can be a valuable tool in the follow-up after this condition.

Farmakis IT; Valerio L; Barco S; Alsheimer E; Ewert R; Hobohm L; Keller K; Germany.; Mavromanoli AC;
Rosenkranz S; Morris TA; Held M; Dumitrescu D;

The European respiratory journal [Eur Respir J] 2023 Mar 23.
Date of Electronic Publication: 2023 Mar 23.

Background: Cardiopulmonary exercise testing (CPET) may provide prognostically valuable information during follow-up after pulmonary embolism (PE).
Objective: To investigate the association of patterns and degree of exercise limitation, as assessed by CPET, with clinical, echocardiographic, laboratory abnormalities and quality of life (QoL) after PE.
Methods: In a prospective cohort study of unselected consecutive all-comers with PE, survivors of the index acute event underwent 3-month and 12-month follow-up, including CPET. We defined cardiopulmonary limitation as ventilatory inefficiency or insufficient cardiocirculatory reserve. Deconditioning was defined as peak VO ₂ <80% with no other abnormality.
Results: Overall, 396 patients were included. At 3 months, prevalence of cardiopulmonary limitation and deconditioning was 50.1% (34.7% mild/moderate; 15.4% severe) and 12.1%, respectively; at 12 months, it was 44.8% (29.1% mild/moderate 15.7% severe) and 14.9%. Cardiopulmonary limitation and its severity were associated with age (OR per decade 2.05; 95% CI 1.65-2.55), history of chronic lung disease (OR 2.72; 95% CI 1.06-6.97), smoking (OR 5.87; 2.44-14.15), and intermediate- or high-risk acute PE (OR 4.36; 95% CI 1.92-9.94). Severe cardiopulmonary limitation at 3 months was associated with the prospectively defined, combined clinical-haemodynamic endpoint of “post-PE impairment” (OR 6.40, 95% CI 2.35-18.45) and with poor disease-specific and generic health-related QoL.
Conclusion: Abnormal exercise capacity of cardiopulmonary origin is frequent after PE, being associated with clinical and hemodynamic impairment as well as long-term QoL reduction. CPET can be considered for selected patients with persisting symptoms after acute PE to identify candidates for closer follow-up and possible therapeutic interventions.

Kominami K; Noda K; Minagawa N; Yonezawa K; Akino M;

Medicine [Medicine (Baltimore)] 2023 Mar 24; Vol. 102 (12), pp. e33356.

Dynamic lung hyperinflation (DLH) caused by air trapping, which increases residual air volume, is a common cause of shortness of breath on exertion in chronic obstructive pulmonary disease (COPD). DLH is commonly evaluated by measuring the decrease in maximal inspiratory volume during exercise, or using the hyperventilation method. However, only few facilities perform these methods, and testing opportunities are limited. Therefore, we investigated the possibility of visually and qualitatively detecting DLH using data from a cardiopulmonary exercise test (CPET). Four men who underwent symptom-limiting CPET were included in this study, including a male patient in his 60s with confirmed COPD, a 50s male long-term smoker, and 2 healthy men in their 20s and 70s, respectively. We calculated the difference between the inspiratory tidal volume (TV I) and expiratory tidal volume (TV E) per breath (TV E-I) from the breath-by-breath data of each CPET and plotted it against the time axis. No decrease in TV E-I was observed in either of the healthy men. However, in the patient with COPD and long-term smoker, TV E-I began to decrease immediately after the initiation of exercise. These results indicate that DLH can be visually detected using CPET data. However, this study was a validation of a limited number of cases, and a comparison with existing evaluation methods and verification of disease specificity are required.