Category Archives: Publications

Risk stratification in cardiomyopathy.

Sinagra G; Carriere C; Clemenza F; Minà C; Bandera F; Zaffalon D; Merlo M; Agostoni P;

European journal of preventive cardiology [Eur J Prev Cardiol] 2020 Dec; Vol. 27 (2_suppl), pp. 52-58.

Prognostic stratification of cardiomyopathies represents a cornerstone for the appropriate management of patients and is focused mainly on arrhythmic events and heart failure. Cardiopulmonary exercise testing provides additional prognostic information, particularly in the setting of heart failure. Cardiopulmonary exercise testing data, integrated in scores such as the Metabolism Exercise Cardiac Kidney Index score have been shown to improve the risk stratification of these patients. Cardiopulmonary exercise testing has been analysed as a potential supplier of prognostic parameters in the context of hypertrophic cardiomyopathy, for which it has been shown that a reduced oxygen consumption peak, an increased ventilation/carbon dioxide production slope and chronotropic incompetence correlate with a worse prognosis. To a lesser extent, in dilated cardiomyopathy, it has been shown that the percentage of oxygen consumption peak, not the pure value, and the ventilation/carbon dioxide production slope are associated with a greater cardiovascular risk. Few data are available about other cardiomyopathies (arrhythmogenic and restrictive). Cardiomyopathy patients should be early and routinely referred to heart failure advanced centres in order to perform a comprehensive risk stratification which should include a cardiopulmonary exercise test, with variables and cut-offs shown to improve their risk stratification.

Roles of periodic breathing and isocapnic buffering period during exercise in heart failure.

Agostoni P; Emdin M; De Martino F; Apostolo A; Masè M; Contini M; Carriere C; Vignati C; Sinagra G;

European journal of preventive cardiology [Eur J Prev Cardiol] 2020 Dec; Vol. 27 (2_suppl), pp. 19-26.

In heart failure, exercise – induced periodic breathing and end tidal carbon dioxide pressure value during the isocapnic buffering period are two features identified at cardiopulmonary exercise testing strictly related to sympathetic activation. In the present review we analysed the physiology behind periodic breathing and the isocapnic buffering period and present the relevant prognostic value of both periodic breathing and the presence/absence of the identifiable isocapnic buffering period.

The MECKI score initiative: Development and state of the art.

Salvioni E; Bonomi A; Re F; Mapelli M; Mattavelli I; Vitale G; Sarullo FM; Palermo P; Veglia F; Agostoni P;

European journal of preventive cardiology [Eur J Prev Cardiol] 2020 Dec; Vol. 27 (2_suppl), pp. 5-11.

The high morbidity and poor survival rates associated with chronic heart failure still represent a big challenge, despite improvements in treatments and the development of new therapeutic opportunities. The prediction of outcome in heart failure is gradually moving towards a multiparametric approach in order to obtain more accurate models and to tailor the prognostic evaluation to the individual characteristics of a single subject. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was developed 10 years ago from 2715 patients and subsequently validated in a different population. The score allows an accurate evaluation of the risk of heart failure patients using only six variables that include the evaluation of the exercise capacity (peak oxygen uptake and ventilation/CO 2 production slope), blood samples (haemoglobin, Na + , Modification of Diet in Renal Disease) and echocardiography (left ventricular ejection fraction). Over the following years, the MECKI score was tested taking into account therapies and specific markers of heart failure, and it proved to be a simple, useful tool for risk stratification and for therapeutic strategies in heart failure patients. The close connection between the centres involved and the continuous updating of the data allow the participating sites to propose substudies on specific subpopulations based on a common dataset and to put together and develop new ideas and perspectives.

Physical activity and cardiorespiratory fitness – a ten year follow-up.

Bahls M; Ittermann T; Ewert R; Stubbe B; Völzke H; Friedrich N; Felix SB; Dörr M;

Scandinavian journal of medicine & science in sports [Scand J Med Sci Sports] 2020 Nov 18. Date of Electronic Publication: 2020 Nov 18.

Physical activity (PA) may influence cardio-respiratory fitness (CRF). Yet, PA takes place in different domains (i.e. sports related physical activity [SPA], leisure time related physical activity [LTPA] and work-related physical activity [WPA]) and not all domain-specific PA may help to maintain high CRF levels throughout life. We assessed the relationship between changes in domain specific PA and the age-related decline in CRF. We analyzed data of 353 men (median age 50 years; inter-quartile range [IQR] 40 to 60) and 335 women (median age 50 years; IQR 41 to 59) with data for domain-specific PA as well as CRF testing measured ten years apart. CRF was assessed with cardiorespiratory exercise testing. Domain specific PA was measured using the Baecke questionnaire. During the 10 year follow-up CRF decreased in men from 29.3 (IQR 25.0 to 34.7) ml/min/kg to 24.3 (IQR 20.8 to 27.3) ml/min/kg. In women CRF declined from 26.0 (IQR 21.0 to 30.9) to 21.4 (IQR 18.3 to 25.6) ml/min/kg. A one point higher SPA at baseline was related to a 1.14 (95% confidence interval [CI] -1.50 to -0.53) ml/min/kg greater decrease in VO 2peak . A one point greater SPA and LTPA over time was associated with a 1.68 (95% CI 1.06 to 2.29) ml/min/kg and 1.24 (95% CI 0.57 to 1.90) ml/min/kg lower decrease in VO 2peak , respectively. Neither baseline values nor changes of WPA were associated with CRF. Sports and leisure time related PA may attenuate the age related decline in CRF.

Central Command and the Regulation of Exercise Heart Rate Response in Heart Failure with Preserved Ejection Fraction.

Sarma S; Howden E; Lawley J; Samels M; Levine BD;

Circulation [Circulation] 2020 Nov 18. Date of Electronic Publication: 2020 Nov 18.

Background: Chronotropic incompetence (CI) is common in HFpEF and is linked to impaired aerobic capacity. Whether upstream autonomic signaling pathways responsible for raising exercise heart rate (HR) are impaired in HFpEF is unknown. We investigated the integrity of central command and muscle metaboreceptor function, two predominant mechanisms responsible for exertional increases in HR, in HFpEF and senior control subjects. Methods: Fourteen healthy, senior controls (7M,7F) and 20 carefully screened HFpEF patients (8M,12F) underwent cardiopulmonary exercise testing (peak VO 2 ) and static handgrip exercise at 40% of maximal voluntary contraction (MVC) to fatigue with post-exercise circulatory arrest (PECA) for 2 minutes to assess central command and metaboreceptor function respectively.
Results: Peak VO 2 (13.1 ± 3.4 vs 22.7 ± 4.0 ml/kg/min; p<0.001) and HR (122 ± 20 vs 155 ± 14 bpm; p<0.001) were lower in HFpEF than senior controls. There were no significant differences in peak HR response during static handgrip between groups (HFpEF vs controls: 90 ± 13 vs 93 ± 10 bpm; p=0.49). Metaboreceptor function defined as mean arterial blood pressure at the end of PECA was also not significantly different between groups.
Conclusions: Central command (vagally mediated) and metaboreceptor function (sympathetically mediated) in patients with HFpEF were not different from healthy senior controls despite significantly lower peak whole-body exercise heart rates. These results demonstrate key reflex autonomic pathways regulating exercise heart rate responsiveness are intact in HFpEF.

Impact of peak respiratory exchange ratio on the prognostic power of symptoms-limited exercise testing using Bruce protocol in patients with Fontan physiology.

Niu J; Godoy A; Kadish T; Das BB;

Cardiology in the young [Cardiol Young] 2020 Nov 19, pp. 1-8. Date of Electronic Publication: 2020 Nov 19.

Objectives: We evaluated the impact of peak respiratory exchange ratio on the prognostic values of cardiopulmonary exercise variables during symptoms-limited incremental exercise tests in patients with Fontan physiology.
Methods: Retrospective single-centre chart review study of Fontan patients who underwent exercise testing using the Bruce protocol between 2014 and 2018 and follow-up.
Results: A total of 34 patients (age > 18 years) had a Borg score of ≥7 on the Borg 10-point scale, but only 50% of patients achieved a peak respiratory exchange ratio of ≥ 1.10 (maximal test). Peak oxygen consumption, percent-predicted peak oxygen consumption, and peak oxygen consumption at the ventilatory threshold was reduced significantly in patients with a peak respiratory exchange ratio of < 1.10. Peak oxygen consumption and percent-predicted peak oxygen consumption was positively correlated with peak respiratory exchange ratio values (r = 0.356, p = 0.039). After a median follow-up of 21 months, cardiac-related events occurred in 16 (47%) patients, with no proportional differences in patients due to their respiratory exchange ratio (odds ratio, 0.62; 95% CI: 0.18-2.58; p = 0.492). Multivariate Cox proportional hazard analysis showed percent-predicted peak oxygen consumption, peak heart rate, and the oxygen uptake efficient slope were highly related to the occurrence of events in patients only with a peak respiratory exchange ratio of ≥ 1.10.
Conclusions: The value of peak cardiopulmonary exercise variables is limited for the determination of prognosis and assessment of interventions in Fontan patients with sub-maximal effort. Our findings deserve further research and clinical application.

Longitudinal changes in exercise capacity among adult cystic fibrosis patients.

Boutou AK; Manika K; Hajimitrova M; Pitsiou G; Giannakopoulou P; Sourla E; Kioumis I;

Advances in respiratory medicine [Adv Respir Med] 2020; Vol. 88 (5), pp. 420-423.

Introduction: Longitudinal data regarding changes in exercise capacity among adult cystic fibrosis (CF) patients are currently scarce. The aim of this brief report was to assess changes in exercise capacity among adult CF patients with stable and mild-to-moderate disease eight years after their initial evaluation.
Material and Methods: Maximum cardiopulmonary exercise testing (CPET) was utilized. Other assessments included Doppler echocardiography, the 6-minute walking test, spirometry, and lung volume evaluation.
Results: Eleven (6 male, 5 female) patients completed both evaluations (initial and after eight years). During follow-up, indices of ventilatory impairment (such as ventilatory reserve; p=0.019, and ventilatory equivalent for carbon dioxide; p = 0.047) deterio-rated significantly following a decline in respiratory function measurements. Peak oxygen uptake (VO2), both as an absolute (26.6 ± 8.46 vs 23.89 ± 6.16 mL/kg/min; p = 0.098) and as a % of predicted value (71.21 ± 16.54 vs 70.60 ± 15.45; p = 0.872), did not deteriorate. This is also true for oxygen pulse (p = 0.743), left heart ejection fraction (p = 0.574), and pulmonary artery systolic pressure (p = 0.441). However, the anaerobic threshold, both as an absolute (p = 0.009) and as a % of predicted value (p = 0.047), was significantly lower during follow-up.
Conclusion: In adult CF patients with stable, mild-to-moderate disease, a peak VO2 may be preserved for several years. However, even in these patients, deconditioning is present.

Prediction Equations for Maximal Aerobic Capacity on Cycle Ergometer for the Spanish Adult Population.

Puente-Maestú L; Ortega F; Pedro JG; Rodríguez-Nieto MJ; Gómez-Seco J; Gáldiz B; Ojanguren I; Muñoz X; Blanco I; Burgos F; Rodríguez-Chiaradía DA; Gea J; García-Rio F;

Archivos de bronconeumologia [Arch Bronconeumol] 2020 Oct 10. Date of Electronic Publication: 2020 Oct 10.

Background: Frequently used reference values for clinical exercise testing have been derived from non-random samples and some with poorly defined maximal criteria. Our objective was to obtain population based reference values for peak oxygen uptake (V˙O 2 ) and work rate (WR) for cardiopulmonary exercise testing in a representative sample of Caucasian Spanish men and women.
Methods: 182 men and women, 20-85 years old, were included and exercised on cycle-ergometer to exhaustion. (V˙O 2 ) and WR were measured. The equations obtained from this sample were validated in an independent cohort of 69 individuals, randomly sampled form the same population. Then a final equation merging the two cohorts (=251) was produced.
Results: Height, sex and age resulted predictive of both V˙O 2 peak and WR. Weight and physical activity added very little to the accuracy to the equations. The formulas V˙O 2 peak=0.017⋅height(cm)-0.023⋅age(years)+0.864⋅sex(female=0/male=1)±179lmin -1 , and peak WR=1.345 · height (cm) – 2.074 · age (years)+76.54 · sex (female=0/male=1)±21.2W were the best compromise between accuracy and parsimony.
Conclusions: This study provides new and accurate V˙O 2 peak and WR rate reference values for individuals of European Spanish descent.

Elevated exercise ventilation in mild COPD is not linked to enhanced central chemosensitivity.

Phillips DB; Domnik NJ; Elbehairy AF; Preston ME; Milne KM; James MD; Vincent SG; Ibrahim-Masthan M; Neder JA; O’Donnell DE;

Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2020 Nov 05, pp. 103571. Date of Electronic Publication: 2020 Nov 05.

Background: The purpose of this study was to determine if altered central chemoreceptor characteristics contributed to the elevated ventilation relative to carbon dioxide production (V̇ E /V̇CO 2 ) response during exercise in mild chronic obstructive pulmonary disease (COPD).
Methods: Twenty-nine mild COPD and 19 healthy age-matched control participants undertook lung function testing followed by symptom-limited incremental cardiopulmonary exercise testing (CPET). On a separate day, basal (non-chemoreflex) ventilation (V̇ EB ), the central chemoreflex ventilatory recruitment threshold for CO 2 (VRTCO 2 ), and central chemoreflex sensitivity (V̇ ES ) were assessed using the modified Duffin’s CO 2 rebreathing method. Resting arterialized blood gas data were also obtained.
Results: At standardized exercise intensities, absolute V̇ E and V̇ E /V̇CO 2 were consistently elevated and the end-tidal partial pressure of CO 2 was relatively decreased in mild COPD versus controls (all p < 0.05). There were no between-group differences in resting arterialized blood gas parameters, basal V̇ E , VRTCO 2 , or V̇ ES (all p > 0.05).
Conclusion: These data have established that excessive exercise ventilation in mild COPD is not explained by altered central chemosensitivity.

Using heart rate to estimate the minute ventilation and inhaled load of air pollutants.

Guo Q; Zhao Y; Shao J; Cao S; Wang Q; Wu W;

The Science of the total environment [Sci Total Environ] 2020 Oct 19, pp. 143011. Date of Electronic Publication: 2020 Oct 19.

Background: The health effects of air pollution are associated with the concentration of pollutants and ventilation (VE). VE is difficult to measure directly and has been predicted by heart rate (HR). However, it is unclear whether equations between HR and VE obtained from a laboratory cardiopulmonary exercise test (CPET) can be extended to external groups and there is still a gap in their relationship for a Chinese population.
Objective: To establish an association between HR and VE in young Chinese individuals and verify the external validity of the model.
Methods: Eighty non-smoking participants aged 16-21 years underwent incremental tests using a bicycle ergometer, where the HR and minute VE were measured simultaneously. Linear mixed models were constructed with data obtained from a CPET. Ten individuals were chosen randomly as the external validation group. The predictive performance was assessed using an eight-fold cross-validation procedure. Air pollution concentration was monitored during the CPET and the inhaled load was calculated.
Results: The overall estimation of the intercept and slope for all participants was 0.585 ± 0.013 and 0.007 ± 0.00002, respectively. The overall fitted R squared (R 2 ) was 0.84. The median difference between the measured VE and the predicted VE was 0.3 L/min, and the difference between the inhaled load based on the fitted VE and the measured VE was 0.0-0.3 μg across all the participants. The eight folds cross-validation R 2 value was 0.78, suggesting high predictive accuracy.
Conclusion: This is the first study to derive a novel equation for the relationship between HR and VE in a young Chinese population and verify its external validity. This will be important in the assessment of the inhaled load in future epidemiology studies. However, inter-individual variations should also be considered when VE is estimated at an individual level.