Sandberg C, Hedström M, Wadell K, Dellborg M, Ahnfelt A,
Zetterström AK, Öhrn A, Johansson B.

Congenit Heart Dis. 2018 Mar;13(2):254-262.

OBJECTIVE: The beneficial effects of exercise training in acquired heart failure
and coronary artery disease are well known and have been implemented in current
treatment guidelines. Knowledge on appropriate exercise training regimes for
adults with congenital heart disease is limited, thus further studies are needed.
The aim of this study was to examine the effect of home-based interval exercise
training on maximal endurance capacity and peak exercise capacity.
DESIGN: Randomized controlled trial.
METHODS: Twenty-six adults with complex congenital heart disease were recruited
from specialized units for adult congenital heart disease. Patients were
randomized to either an intervention group-12 weeks of home-based interval
exercise training on a cycle ergometer (n = 16), or a control group (n = 10). The
latter was instructed to maintain their habitual physical activities. An
incremental cardiopulmonary exercise test and a constant work rate
cardiopulmonary exercise test at 75% of peak workload were performed
preintervention and postintervention.
RESULTS: Twenty-three patients completed the protocol and were followed
(intervention n = 13, control n = 10). Postintervention exercise time at constant
work rate cardiopulmonary exercise test increased in the intervention group
compared to controls (median[range] 12[-4 to 52]min vs 0[-4 to 5]min, P = .001).
At incremental cardiopulmonary exercise test, peak VO2 increased 15% within the
intervention group (P = .019) compared to 2% within the control group (P = .8).
However, in comparison between the groups no difference was found (285[-200 to
535] ml/min vs 17[-380 to 306] ml/min, P = .10). In addition, peak workload at
incremental cardiopulmonary exercise test increased in the intervention group
compared to controls (20[-10 to 70]W vs 0[-20 to 15]W, P = .003).
CONCLUSION: Home-based interval exercise training increased endurance capacity
and peak exercise capacity in adults with complex congenital heart disease.
Aerobic endurance might be more relevant than peak oxygen uptake with regard to
daily activities, and therefore a more clinically relevant measure to evaluate.

Mezzani A; Pistono M; Agostoni P; Giordano A; Gnemmi M; Imparato A; Temporelli P; Corrà U;

Plos One [PLoS One] 2018 Jun 01; Vol. 13 (6), pp. e0187112. Date of Electronic Publication: 20180601 (Print Publication: 2018)

Exercise ventilation/perfusion matching in continuous-flow left ventricular assist device recipients (LVAD) has not been studied systematically. Twenty-five LVAD and two groups of 15 reduced ejection fraction chronic heart failure (HFrEF) patients with peak VO2 matched to that of LVAD (HFrEF-matched) and ≥14 ml/kg/min (HFrEF≥14), respectively, underwent cardiopulmonary exercise testing with arterial blood gas analysis, echocardiogram and venous blood sampling for renal function evaluation. Arterial-end-tidal PCO2 difference (P(a-ET)CO2) and physiological dead space-tidal volume ratio (VD/VT) were used as descriptors of alveolar and total wasted ventilation, respectively. Tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio (TAPSE/PASP) and blood urea nitrogen/creatinine ratio were calculated in all patients and used as surrogates of right ventriculo-arterial coupling and circulating effective volume, respectively. LVAD and HFrEF-matched showed no rest-to-peak change of P(a-ET)CO2 (4.5±2.4 vs. 4.3±2.2 mm Hg and 4.1±1.4 vs. 3.8±2.5 mm Hg, respectively, both p >0.40), whereas a decrease was observed in HFrEF≥14 (6.5±3.6 vs. 2.8±2.0 mm Hg, p <0.0001). Rest-to-peak changes of P(a-ET)CO2 correlated to those of VD/VT (r = 0.70, p <0.0001). Multiple regression indicated TAPSE/PASP and blood urea nitrogen/creatinine ratio as independent predictors of peak P(a-ET)CO2. LVAD exercise gas exchange is characterized by alveolar wasted ventilation, i.e. hypoperfusion of ventilated alveoli, similar to that of advanced HFrEF patients and related to surrogates of right ventriculo-arterial coupling and circulating effective volume.

Yuan P, Ni HJ, Chen TX, Pudasaini B, Jiang R, Liu H, Zhao
QH, Wang L, Gong SG, Liu JM

Hypertens Res. 2017 Oct 5;40(10):868-875. doi: 10.1038/hr.2017.52. Epub 2017 Jun
1.

Cardiopulmonary exercise testing (CPET) has been used for prognosis in idiopathic
pulmonary arterial hypertension (IPAH). We explored whether sex differences had
an impact on prognostic assessments of CPET in IPAH. Data were retrieved from 21
male and 36 female incident IPAH patients who underwent both right heart
catheterization and CPET from 2010 to 2016 at Shanghai Pulmonary Hospital. Cox
proportional hazards analysis was used to assess the prognostic value of CPET.
The mean duration of follow-up was 22±15 months. Nine men and 15 women had an
event. The differences in clinical parameters in the whole population were not
the same as the inter-subgroup differences. Event-free women had significantly
higher cardiac output, lower pulmonary vascular resistance and percentage of
predicted FVC compared with event men (all P<0.05). Event-free men had
significantly higher end-tidal partial pressure of CO2 (PETCO2) at anaerobic
threshold (AT), peak workload, PETCO2, maximum oxygen consumption (VO2)/minute
ventilation (VE), and oxygen uptake efficiency slope and lower end-tidal partial
pressure of O2 (PETO2) at AT, peak PETO2, and lowest VE/VCO2 compared with event
men. Event-free women had dramatically higher peak VO2, VCO2, VE and O2 pulse
than event women (all P<0.05). Peak PETCO2 was the independent predictor of
event-free survival in all patients and males, whereas peak O2 pulse was the
independent predictor of event-free survival in females. Men with peak
PETCO2⩾20.50 mm Hg, women with peak O2 pulse ⩾6.25 ml per beat and all patients
with peak PETCO2⩾27.03 mm Hg had significantly better event-free survival.
Sex-specific CPET parameters are predictors of poor outcomes. Decreased peak
PETCO2 in men and peak O2 pulse in women were associated with lower event-free
survival in IPAH.

Popovic D, Martic D, Djordjevic T, Pesic V, Guazzi M, Myers J,
Mohebi R, Arena R

Int J Cardiol. 2017 Dec 1;248:39-45. doi: 10.1016/j.ijcard.2017.06.107. Epub 2017
Jun 28.

BACKGROUND: Revascularization appears to be beneficial only in patients with high
levels of ischemia. This study examined the utility of gas analysis during the
recovery phase of cardiopulmonary exercise testing (CPET) in predicting coronary
artery disease (CAD) severity and prognosis.
METHODS: 40 Caucasian patients (21.2% females), mean age 63.5±7.6 with
significant coronary artery lesions (≥50%) were studied. Within two months of
coronary angiography, CPET on a treadmill (TM) and recumbent ergometer (RE) were
performed on two visits 2-4days apart; subjects were subsequently followed
32±10months. Myocardial wall motion was recorded by echocardiography at rest and
peak exercise. Ischemia was quantified by the wall motion score index (WMSI).
RESULTS: Mean ejection fraction was 56.7±9.6%. Patients with 1-2 stenotic
coronary arteries (SCA) showed a poorer CPET response during the recovery phase
than patients with 3-SCA. ROC analysis revealed the change of carbon-dioxide
output (∆VCO2) recovery/peak (area under ROC curve 0.77, p=0.02, Sn=87.5%,
Sp=70.4%) and oxygen uptake (∆VO2) recovery/peak during TM CPET (area under ROC
curve 0.76, p=0.03, Sn 75.0%, Sp 77.8%) were significant in distinguishing
between 1-2-SCA and 3-SCA. The same variables predicted ΔWMSI peak/rest on
univariate analysis (p<0.05). Multivariate Cox analysis revealed a high
predictive value of ∆VO2 recovery/peak obtained during TM CPET for composite
endpoint of cumulative cardiac events (HR=1.27, CI=1.07-1.51, p=0.008).
CONCLUSIONS: The current study suggests CPET parameters in recovery hold
predictive value for CAD severity and prognosis. TM testing seems to be a better
approach in the assessment of CAD severity and prognosis.

Layton AM, Armstrong HF, Baldwin MR, Podolanczuk AJ, Pieszchata
NM, Singer JP, Arcasoy SM, Meza KS, D’Ovidio F, Lederer DJ

Respir Med. 2017 Oct;131:70-76. doi: 10.1016/j.rmed.2017.08.010. Epub 2017 Aug
10.

BACKGROUND: Frail lung transplant candidates are more likely to be delisted or
die without receiving a transplant. Further knowledge of what frailty represents
in this population will assist in developing interventions to prevent frailty
from developing. We set out to determine whether frail lung transplant candidates
have reduced exercise capacity independent of disease severity and diagnosis.
METHODS: Sixty-eight adult lung transplant candidates underwent cardiopulmonary
exercise testing (CPET) and a frailty assessment (Fried’s Frailty Phenotype
(FFP)). Primary outcomes were peak workload and peak aerobic capacity (V˙O2). We
used linear regression to adjust for age, gender, diagnosis, and lung allocation
score (LAS).
RESULTS: The mean ± SD age was 57 ± 11 years, 51% were women, 57% had
interstitial lung disease, 32% had chronic obstructive pulmonary disease, 11% had
cystic fibrosis, and the mean LAS was 40.2 (range 19.2-94.5). In adjusted models,
peak workload decreased by 10 W (95% CI 4.7 to 14.6) and peak V˙O2 decreased by
1.8 mL/kg/min (95% CI 0.6 to 2.9) per 1 unit increment in FFP score. After
adjustment, exercise tolerance was 38 W lower (95% CI 18.4 to 58.1) and peak V˙O2
was 8.5 mL/kg/min lower (95% CI 3.3 to 13.7) among frail participants compared to
non-frail participants. Frailty accounted for 16% of the variance (R2) of watts
and 19% of the variance of V˙O2 in adjusted models.
CONCLUSION: Frailty contributes to reduced exercise capacity among lung
transplant candidates independent of disease severity.

Sharma A, Stevens SR, Lucas J, Fiuzat M, Adams KF, Whellan DJ,
Donahue MP, Kitzman DW, Piña IL, Zannad F, Kraus WE, O’Connor
CM, Felker GM

JACC Heart Fail. 2017 Oct;5(10):724-734

OBJECTIVES: This study sought to determine the relationship between growth
differentiation factor (GDF)-15 and clinical outcomes in ambulatory patients with
heart failure and reduced ejection fraction (HFrEF).
BACKGROUND: The prognostic utility of GDF-15, a member of the transforming growth
factor-β cytokine family, among patients with HF is unclear.
METHODS: We assessed GDF-15 levels in 910 patients enrolled in the HF-ACTION
(Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training)
trial, a randomized clinical trial of exercise training in patients with HFrEF.
Median follow-up was 30 months. Cox proportional hazard models assessed the
relationships between GDF-15 and clinical outcomes.
RESULTS: The median GDF-15 concentration was 1,596 pg/ml. Patients in the highest
tertile of GDF-15 were older and had measurements of more severe HF (higher
N-terminal pro-B-type natriuretic peptide [NT-proBNP] concentrations and lower
peak oxygen uptake on cardiopulmonary exercise testing [CPX]). GDF-15 therapy was
a significant predictor of all-cause death (unadjusted hazard ratio [HR]: 2.03
when GDF-15 was doubled; p < 0.0001). This association persisted after adjustment
for demographic and clinical and biomarkers including high sensitivity troponin T
(hs-TnT) and NT-proBNP (HR: 1.30 per doubling of GDF-15; p = 0.029). GDF-15 did
not improve discrimination (as measured by changes in c-statistics and
the integrated discrimination improvement) in addition to baseline variables,
including hs-TnT and NT-proBNP or variables found in CPX testing.
CONCLUSIONS: In demographically diverse, well-managed patients with HFrEF, GDF-15
therapy provided independent prognostic information in addition to established
predictors of outcomes. These data support a possible role for GDF-15 in the risk
stratification of patients with chronic HFrEF. (Heart Failure: A Controlled Trial
Investigating Outcomes of Exercise Training [HF-ACTION]; NCT00047437)

Avramidou V, Hatziagorou E, Kampouras A, Hebestreit H, Kourouki E,
Kirvassilis F, Tsanakas J

Pediatr Pulmonol. 2018 Jan;53(1):81-87. doi: 10.1002/ppul.23833. Epub 2017 Sep
26.

INTRODUCTION: FEV1 is often considered the gold standard to monitor lung disease
in cystic fibrosis (CF). Recently, there has been increasing interest in multiple
breath washout (MBW) and cardiopulmonary exercise testing (CPET) as alternative
or even more sensitive techniques. However, limited data exist on associations
among the above methods.
AIM: To evaluate the correlations between outcome measures of MBW and CPET and to
examine if ventilation inhomogeneity can predict exercise intolerance.
SUBJECTS AND METHODS: Ninety-seven children and adults with CF (47 males, mean
[range] age 14.9 (6.6; 26.7) years, mean FEV1 : 90.8% predicted, mean lung
clearance index [LCI]: 11.4, and mean peak oxygen uptake [VO2 peak]: 82.4%
predicted) performed spirometry, MBW, and CPET on the same day during their
admission or outpatient visit.
RESULTS: LCI, m1 /m0 , and m2 /m0 (P < 0.001) as well as VO2 peak%, breathing
reserve (BR), minute ventilation (VE)/VO2 (P < 0.001), and VE/carbon dioxide
release (VCO2 ) (P = 0.006) correlated significantly with FEV1 %. LCI, m1 /m0 ,
and m2 /m0 correlated with VO2 peak (P ≤ 0.001), VE (L/min) (P < 0.05), BR
(P < 0.01), VE/VO2 (P < 0.001), and VE/VCO2 (P < 0.01). Multiple regression
analysis showed that LCI could predict BR% (P < 0.001, r2 :0.272) and VE/VO2
(P < 0.001, r2 : 0.207) while LCI and FRC could predict VO2 peak% P < 0.001, r2 :
0.216) and VE/VCO2 (P < 0.001, r2 : 0.226).
CONCLUSION: Ventilation inhomogeneity as indicated by increased LCI is associated
with less efficient ventilation during strenuous exercise and negatively impacts
exercise capacity in CF.

Williams CA, Tomlinson OW, Chubbock LV, Stevens D, Saynor
ZL, Oades PJ, Barker AR

Pediatr Pulmonol. 2018 Jan;53(1):36-42. doi: 10.1002/ppul.23896. Epub 2017 Oct
24.

BACKGROUND: Maximal cardiopulmonary exercise testing is recommended on an annual
basis for children with cystic fibrosis (CF), due to clinically useful prognostic
information provided by maximal oxygen uptake (V̇ O2max ). However, not all
patients are able, or willing, to reach V̇O2max , and therefore submaximal
alternatives are required. This study explored the validity of the oxygen uptake
efficiency slope (OUES) as a submaximal measure of V̇O2max in children and
adolescents with CF.
METHODS: Data were collated from 72 cardiopulmonary exercise tests (36 CF, 36
controls), with OUES determined relative to maximal and submaximal parameters of
exercise intensity, time, and individual metabolic thresholds. Pearson’s
correlation coefficients, independent t-tests, and factorial ANOVAs were used to
determine validity.
RESULTS: Significant (P < 0.05) correlations with V̇O2max were observed for most
expressions of OUES, but were consistently weaker in CF (r = 0.30-0.47) when
compared to CON (r = 0.58-0.89). Mean differences for all OUES parameters between
groups were not significant (P > 0.05). When split by V̇O2max tertiles, minimal
significant differences were found between, and within, groups for OUES,
indicating poor discrimination of V̇O2max .
CONCLUSIONS: The OUES is not a valid (sub) maximal measure of V̇O2max in children
and adolescents with mild-to-moderate CF. Clinicians should continue to use
maximal markers (ie, V̇O2max ) of exercise capacity.

Aguiar Rosa S; Agapito A; Soares RM; Sousa L; Oliveira JA; Abreu A; Silva AS; Alves S; Aidos H; Pinto FF; Ferreira RC;

Revista Portuguesa De Cardiologia: Orgao Oficial Da Sociedade Portuguesa De Cardiologia = Portuguese Journal Of Cardiology: An Official Journal Of The Portuguese Society Of Cardiology [Rev Port Cardiol] 2018 May 15. Date of Electronic Publication: 2018 May 15.

Aim: The aim of the study was to compare functional capacity in different types of congenital heart disease (CHD), as assessed by cardiopulmonary exercise testing (CPET).
Methods: A retrospective analysis was performed of adult patients with CHD who had undergone CPET in a single tertiary center. Diagnoses were divided into repaired tetralogy of Fallot, transposition of the great arteries (TGA) after Senning or Mustard procedures or congenitally corrected TGA, complex defects, shunts, left heart valve disease and right ventricular outflow tract obstruction.
Results: We analyzed 154 CPET cases. There were significant differences between groups, with the lowest peak oxygen consumption (VO2) values seen in patients with cardiac shunts (39% with Eisenmenger physiology) (17.2±7.1ml/kg/min, compared to 26.2±7.0ml/kg/min in tetralogy of Fallot patients; p<0.001), the lowest percentage of predicted peak VO2 in complex heart defects (50.1±13.0%) and the highest minute ventilation/carbon dioxide production slope in cardiac shunts (38.4±13.4). Chronotropism was impaired in patients with complex defects. Eisenmenger syndrome (n=17) was associated with the lowest peak VO2 (16.9±4.8 vs. 23.6±7.8ml/kg/min; p=0.001) and the highest minute ventilation/carbon dioxide production slope (44.8±14.7 vs. 31.0± 8.5; p=0.002). Age, cyanosis, CPET duration, peak systolic blood pressure, time to anaerobic threshold and heart rate at anaerobic threshold were predictors of the combined outcome of all-cause mortality and hospitalization for cardiac cause.
Conclusion: Across the spectrum of CHD, cardiac shunts (particularly in those with Eisenmenger syndrome) and complex defects were associated with lower functional capacity and attenuated chronotropic response to exercise.

D’Andrea A; Radmilovic J; Caselli S; Carbone A; Scarafile R; Sperlongano S; Tocci G; Formisano T; Martone F; Liccardo B; D’Alto M; Bossone E; Galderisi M; Golino P;

The International Journal Of Cardiovascular Imaging [Int J Cardiovasc Imaging] 2018 May 22. Date of Electronic Publication: 2018 May 22.

Anabolic-androgenic steroids (AAS) are used by power athletes to improve performance. However, the real effects of the chronic consumption of AAS on cardiovascular structures are subjects of intense debate. To detect by speckle tracking echocardiography (STE) underlying left atrial (LA) dysfunction in athletes abusing AAS and assess possible correlation between LA myocardial function and exercise capacity during cardiopulmonary stress test. 65 top-level competitive bodybuilders were selected (45 males), including 35 athletes misusing AAS for at least 5 years (users), 30 anabolic-free bodybuilders (non-users), compared to 40 age- and sex-matched healthy sedentary controls. Standard Doppler echocardiography, STE analysis and bicycle ergometric test were performed to assess LA myocardial function and exercise capacity. Athletes showed increased left ventricular (LV) mass index, wall thickness and stroke volume compared with controls, whereas LV ejection fraction, LV end-diastolic diameter and transmitral Doppler indexes were comparable between the three groups. Conversely, LA volume index, LV and LA strain and LV E/Em were significantly increased in AAS users. By multivariate analyses, LV E/Em (beta = - 0.30, p < 0.01), LA volume index (- 0.42, p < 0.001) and number of weeks of AAS use per year (- 0.54, p < 0.001) emerged as the only independent determinants of LA lateral wall peak STE. In addition, a close association between LA myocardial function and VO2 peak during cardiopulmonary exercise testing was evidenced (p < 0.001), showing a powerful incremental value with respect to clinical and standard echocardiographic data. STE represents a promising technique to assess LA myocardial function in athletes abusing steroids. AAS users showed a more impaired LA deformation, associated with reduced functional capacity during physical effort.