Author Archives: Paul Older

Early outcomes of “low-risk” patients undergoing lung resection assessed by cardiopulmonary exercise testing: Single-institution experience.

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.

Ventilatory Threshold and Risk of Pulmonary Exacerbations in Cystic Fibrosis.

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.

Maximal Exercise Improves the Levels of Endothelial Progenitor Cells in Heart Failure Patients.

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.

Correlation between acylcarnitine/free carnitine ratio and cardiopulmonary exercise test parameters in patients with incident dialysis.

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.

Cardiopulmonary Exercise Testing in Children and Young Adolescents after a Multisystem Inflammatory Syndrome: Physical Deconditioning or Residual Pathology?

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.

Cardiopulmonary exercise testing in the follow-up after acute pulmonary embolism.

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.

The concept of detection of dynamic lung hyperinflation using cardiopulmonary exercise testing.

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.

Mechanical dispersion is a superior echocardiographic feature to predict exercise capacity in preclinical and overt heart failure with preserved ejection fraction.

Hortegal RA; Hossri C; Giolo L;   R; Gun C; Assef J; Moriya HT; Franchini KG; Feres F; Meneghelo R;

The international journal of cardiovascular imaging [Int J Cardiovasc Imaging] 2023 Mar 31.
Date of Electronic Publication: 2023 Mar 31.

Background: Heart Failure with Preserved Ejection Fraction (HFpEF) is a syndrome characterized by different degrees of exercise intolerance, which leads to poor quality of life and prognosis. Recently, the European score (HFA-PEFF) was proposed to standardize the diagnosis of HFpEF. Even though Global Longitudinal Strain (GLS) is a component of HFA-PEFF, the role of other strain parameters, such as Mechanical Dispersion (MD), has yet to be studied. In this study, we aimed to compare MD and other features from the HFA-PEFF according to their association with exercise capacity in an outpatient population of subjects at risk or suspected HFpEF.
Methods: This is a single-center cross-sectional study performed in an outpatient population of 144 subjects with a median age of 57 years, 58% females, referred to the Echocardiography and Cardiopulmonary Exercise Test to investigate HFpEF.
Results: MD had a higher correlation to Peak VO2 (r=-0.43) when compared to GLS (r=-0.26), MD presented a significant correlation to Ventilatory Anaerobic Threshold (VAT) (r=-0.20; p = 0.04), while GLS showed no correlation (r=-0.14; p = 0.15). Neither MD nor GLS showed a correlation with the time to recover VO2 after exercise (T1/2). In Receiver Operator Characteristic (ROC) analysis, MD presented superior performance to GLS to predict Peak VO2 (AUC: 0.77 vs. 0.62), VAT (AUC: 0.61 vs. 0.57), and T1/2 (AUC: 0.64 vs. 0.57). Adding MD to HFA-PEFF improved the model performance (AUC from 0.77 to 0.81).
Conclusion: MD presented a higher association with Peak VO2 when compared to GLS and most features from the HFA-PEFF. Adding MD to the HFA-PEFF improved the model performance.

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.