Birkey T; Dixon J; Jacobsen R; Ginde S; Nugent M; Yan K; Simpson P; Kovach J

Pediatric Cardiology. 39(7):1468-1475, 2018 Oct.

Adult congenital heart disease (ACHD) patients often require repeat
cardiothoracic surgery, which may result in significant morbidity and
mortality. Currently, there are few pre-operative risk assessment tools
available. In the general adult population, pre-operative cardiopulmonary
exercise testing (CPET) has a predictive value for post-operative
morbidity and mortality following major non-cardiac surgery. The utility
of CPET for risk assessment in ACHD patients requiring cardiothoracic
surgery has not been evaluated. Retrospective chart review was conducted
on 75 ACHD patients who underwent CPET less than 12 months prior to major
cardiothoracic surgery at Children’s Hospital of Wisconsin. Minimally
invasive procedures, cardiomyopathy, acquired heart disease, single
ventricle physiology, and heart transplant patients were excluded.
Demographic information, CPET results, and peri-operative surgical data
were collected. The study population was 56% male with a median age of 25
years (17-58). Prolonged post-operative length of stay correlated with
increased ventilatory efficiency slope (VE/[Formula: see text] slope) (P =
0.007). Prolonged intubation time correlated with decreased peak HR (P =
0.008), decreased exercise time (P = 0.002), decreased heart rate response
(P = 0.008) and decreased relative peak oxygen consumption (P = 0.034).
Post-operative complications were documented in 59% of patients. While
trends were noted between post-operative complications and some
measurements of exercise capacity, none met statistical significance.
Future studies may further define the relationship between exercise
capacity and post-operative morbidity in ACHD patients.

Suryanegara J; Cassidy S; Ninkovic V; Popovic D; Grbovic M; Okwose N;
Trenell MI; MacGowan GG; Jakovljevic DG.

Acta Diabetologica. 56(3):321-329, 2019 Mar.

AIM: The present study assessed the effect of high intensity interval
training on cardiac function during prolonged submaximal exercise in
patients with type 2 diabetes.
METHODS: Twenty-six patients with type 2 diabetes were randomized to a 12
week of high intensity interval training (3 sessions/week) or standard
care control group. All patients underwent prolonged (i.e. 60 min)
submaximal cardiopulmonary exercise testing (at 50% of previously assess
maximal functional capacity) with non-invasive gas-exchange and
haemodynamic measurements including cardiac output and stroke volume
before and after the intervention.
RESULTS: At baseline (prior to intervention) there was no significant
difference between the intervention and control group in peak exercise
oxygen consumption (20.3 +/- 6.1 vs. 21.7 +/- 5.5 ml/kg/min, p = 0.21),
and peak exercise heart rate (156.3 +/- 15.0 vs. 153.8 +/- 12.5 beats/min,
p = 0.28). During follow-up assessment both groups utilized similar amount
of oxygen during prolonged submaximal exercise (15.0 +/- 2.4 vs. 15.2 +/-
2.2 ml/min/kg, p = 0.71). However, cardiac function i.e. cardiac output
during submaximal exercise decreased significantly by 21% in exercise
group (16.2 +/- 2.7-12.8 +/- 3.6 L/min, p = 0.03), but not in the control
group (15.7 +/- 4.9-16.3 +/- 4.1 L/min, p = 0.12). Reduction in exercise
cardiac output observed in the exercise group was due to a significant
decrease in stroke volume by 13% (p = 0.03) and heart rate by 9% (p =
0.04).
CONCLUSION: Following high intensity interval training patients with type
2 diabetes demonstrate reduced cardiac output during prolonged submaximal
cardiopulmonary exercise testing. Ability of patients to maintain
prolonged increased metabolic demand but with reduced cardiac output
suggests cardiac protective role of high intensity interval training in
type 2 diabetes.

Imboden MT; Harber MP; Whaley MH; Finch WH; Bishop DL; Fleenor BS;
Kaminsky LA.

Progress in Cardiovascular Diseases. 62(2):157-162, 2019 Mar – Apr.

BACKGROUND: The relationship between cardiorespiratory fitness (CRF) and
mortality risk has typically been assessed using a single measurement,
though some evidence suggests the change in CRF over time influences risk.
This evidence is predominantly based on studies using estimated CRF
(CRFe). The strength of this relationship using change in directly
measured CRF over time in apparently healthy men and women is not well
understood.
PURPOSE: To examine the association of change in CRF over time, measured
using cardiopulmonary exercise testing (CPX), with all-cause and
disease-specific mortality and to compare baseline and subsequent CRF
measurements as predictors of all-cause mortality.
METHODS: Participants included 833 apparently healthy men and women
(42.9+/-10.8years) who underwent two maximal CPXs, the second CPX being
>=1year following the baseline assessment (mean 8.6years, range 1.0 to
40.3years). Participants were followed for up to 17.7 (SD 11.8)years for
all-cause-, cardiovascular disease- (CVD), and cancer mortality.
Cox-proportional hazard models were performed to determine the association
between the change in CRF, computed as visit 1 (CPX1) peak oxygen
consumption (VO2peak [mL.kg-1.min-1]) – visit 2 (CPX2) VO2peak, and
mortality outcomes. A Wald-Chi square test of equality was used to compare
the strength of CPX1 to CPX2 VO2peak in predicting mortality.
RESULTS: During follow-up, 172 participants died. Overall, the change in
CPX-CRF was inversely related to all-cause, CVD, and cancer mortality
(p<0.05). Each 1mL.kg-1.min-1 increase was associated with a ~11, 15, and
16% (all p<0.001) reduction in all-cause, CVD, and cancer mortality,
respectively. The inverse relationship between CRF and all-cause mortality
was significant (p<0.05) when men and women were examined independently,
after adjusting for years since first CPX, baseline VO2peak, and age.
Further, the Wald Chi-square test of equality found CPX2 VO2peak to be a
significantly stronger predictor of all-cause mortality than CPX1 VO2peak
(p<0.05).
CONCLUSION: The change in CRF over time was inversely related to
mortality outcomes, and mortality was better predicted by CRF measured at
subsequent test than CPX1 CRF. These findings emphasize the importance of
adopting lifestyle behaviors that promote CRF, as well as support the need
for routine assessment of CRF in clinical practice to better assess risk.

Kaminsky LA; Arena R; Ellingsen O; Harber MP; Myers J; Ozemek C; Ross R

Progress in Cardiovascular Diseases. 62(2):86-93, 2019 Mar – Apr.

The importance of cardiorespiratory fitness (CRF) is now well established
and it is increasingly being recognized as an essential variable which
should be assessed in health screenings. The key findings that have
established the clinical significance of CRF are reviewed in this report,
along with an overview of the current relevance of exercise as a form of
medicine that can provide a number of positive health outcomes, including
increasing CRF. Current assessment options for assessing CRF are also
reviewed, including the direct measurement via cardiopulmonary exercise
testing which now can be interpreted with age and sex-specific reference
values. Future directions for the use of CRF and related measures are
presented.

Bar-Yoseph R; Mandel H; Mainzer G; Gur M; Tal G; Shalloufeh G; Bentur L.

Pediatric Pulmonology. 53(3):366-373, 2018 03.

INTRODUCTION: Enzyme replacement therapy (ERT) with Myozyme improved the
prospect of Pompe disease patients. Our aim was to evaluate ERT acute
effect on exercise capacity in pediatric Pompe patients.

METHODS: Five Pompe patients (10-19 years, 4 infantile-onset and 1
diagnosed at 5 years) were evaluated before and 2 days after ERT using
cardiopulmonary exercise testing (CPET), 6 min walking test (6MWT) and
motor function test (GMFM-88).

RESULTS: Preserved normal peak oxygen uptake, 6MWT and motor function
were observed in the relative mild disease and impairment of these
parameters in the more advanced disease. Two days following ERT, three
patients demonstrated changes; one patient (relative mild disease)
increased both oxygen uptake (11%) and walking distance (38%). Second
patient (advanced disease) increased oxygen uptake (11%) while a small
decrease in walking distance in the 6MWT (8%) was observed. Third patient
(advanced disease) decreased oxygen uptake (39%) but increased walking
distance (42%) and motor function score (27%).

CONCLUSIONS: CPET is safe for pediatric Pompe patients. ERT may benefit
exercise capacity in patients with less advanced disease. Individualized
assessment by CPET, 6MWT, and motor function may help ERT adjustment by
providing precise quantification of the response to treatment. Additional
studies are needed to clarify the benefit of this assessment protocol.

Onofre T; Oliver N; Carlos R; Felismino A; Corte RC; Silva E; Bruno S.

PLoS ONE [Electronic Resource]. 12(4):e0172894, 2017.

Cardiopulmonary assessment through oxygen uptake efficiency slope (OUES)
data has shown encouraging results, revealing that we can obtain important
clinical information about functional status. Until now, the use of OUES
has not been established as a measure of cardiorespiratory capacity in an
obese adult population, only in cardiac and pulmonary diseases or
pediatric patients. The aim of this study was to characterize submaximal
and maximal levels of OUES in a sample of morbidly obese women and analyze
its relationship with traditional measures of cardiorespiratory fitness,
anthropometry and pulmonary function.
Thirty-three morbidly obese women
(age 39.1 +/- 9.2 years) performed Cardiopulmonary Exercise Testing (CPX)
on a treadmill using the ramp protocol. In addition, anthropometric
measurements and pulmonary function were also evaluated. Maximal and
submaximal OUES were measured, being calculated from data obtained in the
first 50% (OUES50%) and 75% (OUES75%) of total CPX duration. In one-way
ANOVA analysis, OUES did not significantly differ between the three
different exercise intensities, as observed through a Bland-Altman
concordance of 58.9 mL/min/log(L/min) between OUES75% and OUES100%, and
0.49 mL/kg/min/log(l/min) between OUES/kg75% and OUES/kg100%. A strong
positive correlation between the maximal (r = 0.79) and submaximal (r =
0.81) OUES/kg with oxygen consumption at peak exercise (VO2peak) and
ventilatory anaerobic threshold (VO2VAT) was observed, and a moderate
negative correlation with hip circumference (r = -0.46) and body adiposity
index (r = -0.50) was also verified. There was no significant difference
between maximal and submaximal OUES, showing strong correlations with each
other and oxygen consumption (peak and VAT).
These results indicate that
OUES can be a useful parameter which could be used as a cardiopulmonary
fitness index in subjects with severe limitations to perform CPX, as for
morbidly obese women.

Dirou S; Chambellan A; Chevallier P; Germaud P; Lamirault G; Gourraud PA;
Perrot B; Delasalle B; Forestier B; Guillaume T; Peterlin P; Garnier A;
Magnan A; Blanc FX; Lemarchand P.

Bone Marrow Transplantation. 53(3):281-290, 2018 03.

Long-term survivors after allogeneic hematopoietic stem cell
transplantation (allo-HSCT) are at high risk for treatment-related adverse
events, that may worsen physical capacity and may induce fatigue and
disability. The aims of this prospective study were to evaluate exercise
capacity in allotransplant survivors and its relationship with fatigue and
disability. Patient-reported outcomes and exercise capacity were evaluated
in 71 non-relapse patients 1 year after allo-HSCT, using validated
questionnaires, cardiopulmonary exercise testing (CPET) with measure of
peak oxygen uptake (peakVO2) and deconditioning, pulmonary function
testing, echocardiography and 6-min walk test. A high proportion (75.4%)
of allo-HSCT survivors showed abnormal cardiopulmonary exercise testing
parameters as compared to predicted normal values, including 49.3%
patients who exhibited moderate to severe impairment in exercise capacity
and 37.7% patients with physical deconditioning. PeakVO2 values were not
accurately predicted by 6-min walk distances (r = 0.53). Disability and
fatigue were strongly associated with decreased peakVO2 values (p = 0.002
and p = 0.008, respectively). Exercise capacity was reduced in most
allo-HSCT long-term survivors. Because reduced exercise capacity was
associated with fatigue, disability and a decrease in quality of life,
cardiopulmonary exercise testing should be performed in every patient who
reports fatigue and disability.

Chaudhry S; Arena R; Bhatt DL; Verma S; Kumar N.

Current Opinion in Cardiology. 33(2):168-177, 2018 03.

PURPOSE OF REVIEW: There is growing clinical interest for the use of
cardiopulmonary exercise testing (CPET) to evaluate patients with or
suspected coronary artery disease (CAD). With mounting evidence, this
concise review with relevant teaching cases helps to illustrate how to
integrate CPET data into real world patient care.
RECENT FINDINGS: CPET provides a novel and purely physiological basis to
identify cardiac dysfunction in symptomatic patients with both
obstructive-CAD and nonobstructive-CAD (NO-CAD). In many cases, abnormal
cardiac response on CPET may be the only objective evidence of potentially
undertreated ischemic heart disease. When symptomatic patients have NO-CAD
on coronary angiogram, they are still at increased risk for cardiovascular
events. This problem appears to be more common in women than men and may
warrant more aggressive risk factor modification. As the main intervention
is lifestyle (diet, smoking cessation, exercise) and medical therapy
(statins, angiotensin-converting enzyme inhibitors, beta-blockers), serial
CPET testing enables close surveillance of cardiovascular function and is
responsive to clinical status.
SUMMARY: CPET can enhance outpatient evaluation and management of CAD.
Diagnostically, it can help to identify physiologically significant
obstructive-CAD and NO-CAD in patients with normal routine cardiac
testing. CPET may be of particular value in symptomatic women with NO-CAD.
Prognostically, precise quantification of improvements in exercise
capacity may help to improve long-term lifestyle and medication adherence
for this chronic condition.

Ascha M; Bhattacharyya A; Ramos JA; Tonelli AR.

Medicine & Science in Sports & Exercise. 50(10):1992-1997, 2018 Oct.
VI 1

INTRODUCTION/PURPOSE: Peripheral capillary oxygen saturation (SpO2) is
used as surrogate for arterial blood oxygen saturation. We studied the
degree of discrepancy between SpO2 and arterial oxygen (SaO2) and
identified parameters that may explain this difference.
METHODS: We included patients who underwent cardiopulmonary exercise
testing at Cleveland Clinic. Pulse oximeters with forehead probes measured
SpO2 and arterial blood gas samples provided the SaO2 both at rest and
peak exercise.
RESULTS: We included 751 patients, 54 +/- 16 yr old with 53% of female
gender. Bland-Altman analysis revealed a bias of 3.8% with limits of
agreement of 0.3% to 7.9% between SpO2 and SaO2 at rest. A total of 174
(23%) patients had SpO2 >= 5% of SaO2, and these individuals were older,
current smokers with lower forced expiratory volume in the first second
and higher partial pressure of carbon dioxide and carboxyhemoglobin. At
peak exercise (n = 631), 75 (12%) SpO2 values were lower than the SaO2
determinations reflecting difficulties in the SpO2 measurement in some
patients. The bias between SpO2 and SaO2 was 2.6% with limits of agreement
between -2.9% and 8.1%. Values of SpO2 >= 5% of SaO2 (n = 78, 12%) were
associated with the significant resting variables plus lower heart rate,
oxygen consumption, and oxygen pulse. In multivariate analyses,
carboxyhemoglobin remained significantly associated with the difference
between SpO2 and SaO2 both at rest and peak exercise.
CONCLUSIONS: In the present study, pulse oximetry commonly overestimated
the SaO2. Increased carboxyhemoglobin levels are independently associated
with the difference between SpO2 and SaO2, a finding particularly relevant
in smokers.

Wagner J; Agostoni P; Arena R; Belardinelli R; Dumitrescu D; Hager A;
Myers J; Rauramaa R; Riley M; Takken T; Schmidt-Trucksass A.

American Heart Journal. 202:116-126, 2018 08.
VI 1

Heart failure with reduced ejection fraction (HFrEF) is common in the
developed world and results in significant morbidity and mortality.
Accurate risk assessment methods and prognostic variables are therefore
needed to guide clinical decision making for medical therapy and surgical
interventions with the ultimate goal of decreasing risk and improving
health outcomes. The purpose of this review is to examine the role of
cardiopulmonary exercise testing (CPET) and its most commonly used
ventilatory gas exchange variables for the purpose of risk stratification
and management of HFrEF. We evaluated five widely studied gas exchange
variables from CPET in HFrEF patients based on nine previously used
systematic criteria for biomarkers. This paper provides clinicians with a
comprehensive and critical overview, class recommendations and evidence
levels. Although some CPET variables met more criteria than others,
evidence supporting the clinical assessment of variables beyond peak VO2
is well-established. A multi-variable approach also including the VE-VCO2
slope and EOV is therefore recommended.