Agnoletti G, Gala S, Ferroni F, Bordese R, Appendini L, Pace, Napoleone C, Bergamasco L;

J Thorac Cardiovasc Surg. 2017 Jun;153(6):1468-1475. doi:
10.1016/j.jtcvs.2017.01.051. Epub 2017 Feb 10.

Comment in
J Thorac Cardiovasc Surg. 2017 Jun;153(6):1476-1478.
J Thorac Cardiovasc Surg. 2017 Jun;153(6):1466-1467.

OBJECTIVES: To evaluate the effects of endothelin inhibitors (ERAs) on
hemodynamic and functional parameters in patients post-Fontan procedure with high
pulmonary vascular resistance (PVR).
METHODS: Among our cohort of patients with Fontan circulation, 8 children, 8
adolescents, and 8 adults had PVR ≥2 WU*m2. These patients were treated with ERAs
(minors with bosentan, adults with macitentan) and reevaluated after 6 months.
Pre- and posttreatment hemodynamic variables were assessed by cardiac
catheterization. Functional capacity was evaluated by cardiopulmonary exercise
testing (CPET). Our primary endpoint was to obtain a reduction of PVR; the
secondary endpoint was to obtain an improvement of functional capacity.
RESULTS: Under treatment, New York Heart Association class improved for
adolescents and adults. PVR decreased (P = .01) in all groups: in children from
the median value 2.3 (interquartile range 2.0-3.1) to 1.9 (1.4-2.3) WU*m2, in
adolescents from 2.3 (2.1-2.4) to 1.7 (1.4-1.8) WU*m2, and in adults from 2.8
(2.0-4.7) to 2.1 (1.8-2.8)WU*m2. In 71% of patients, PVR fell to less than 2
WU*m2. Cardiac index increased in adolescents from 2.6 (2.4-3.3) to 3.6 (3.4-4.3)
L/min/m2, P = .04, and in adults from 2.1 (2.0-2.3) to 2.8 (2.3-4.7) L/min/m2,
P = .03. CPET showed that only adolescents displayed a significant functional
improvement. Anaerobic threshold improved from 17 (13-19) to 18 (13-20)
mL/kg/min, P = .03; oxygen consumption and VO2 max increased from 1.3 (1.0-1.6)
to 1.7 (1.1-1.9) L/min, P = .02 and from 25 (21-28) to 28 (26-31) L/min, P = .02,
respectively. Oxygen pulse increased from 7.9 (5.7-10.4) to 11.2 (8.2-13.0)
L/beat, P = .01.
CONCLUSIONS: This is the first study that assesses by cardiac catheterization and
CPET the effects of ERA in patients with Fontan circulation with increased PVR.
These results suggest that ERAs might provide most pronounced hemodynamic and
functional improvement in adults and adolescents.

Fisher O, Gates Z, Parkes E, Shakespeare J, Goodyear SJ, Imray CHE, Benson RA;

Ann Vasc Surg. 2019 Aug 5. pii: S0890-5096(19)30542-4. doi:
10.1016/j.avsg.2019.05.047. [Epub ahead of print]

INTRODUCTION: Cardiopulmonary exercise testing (CPET) provides an objective
assessment of functional capacity and fitness. It can be used to guide decision
making prior to major vascular surgery. The EVAR-2 trial suggested endovascular
aneurysm repair (EVAR) in patients unfit for open repair failed to provide a
significant survival advantage over non surgical management. The aim of this
study was to assess contemporary survival differences between patients with poor
CPET measures who underwent EVAR or were not offered surgical intervention.
METHODS: A prospectively maintained database of CPET results of patients
considered for elective infrarenal aortic aneurysm repair was interrogated.
Anaerobic threshold (AT) of <11ml/min/kg was used to indicate poor physical
fitness. Hospital electronic records were then reviewed for peri-operative,
re-intervention and long term outcomes.
RESULTS: Between November 2007 and October 2017 532 aortic aneurysm repairs were
undertaken, of which 376 underwent pre-operative CPET. 70 patients were
identified as having an AT<11ml/min/kg. 37 patients underwent EVAR and 33 were
managed non surgically. All cause survival at 1, 3 and 5 years for those patients
who underwent EVAR was 97% 92% and 81% respectively. For those not offered
surgical intervention survival at the same points was 72%, 48% and 24% HR=5.13
(1.67-15.82) p=0.004. Aneurysm specific survival at 1, 3 and 5 years for those
patients who underwent EVAR was 97% 94% and 94% respectively. Survival at the
same time points for those not offered surgical intervention was 90% 69% 39%.
HR=7.48 (1.37-40.82) p=0.02.
CONCLUSIONS: In this small, retrospective, single centre, non-randomised cohort
EVAR may provide a survival advantage in patients with poor physical fitness
identified via CPET. Randomised studies with current generation EVAR are required
to validate the results shown here. Risk prediction, CPET, Survival.

Agostoni P, Dumitrescu D.

International Journal of Cardiology 288 (2019) 107–113

In the present practice review, we will explain how to perform and interpret a cardiopulmonary exercise test
(CPET) in heart failure patients. Specifically, we will explain why cycle ergometer should be preferred to treadmill,
the type of protocol needed, and the ideal exercise duration. Thereafter, we will discuss how to interpret
CPET findings and determine the parameters that should be included.Wewill focus specifically on: peak VO2 (absolute value and a percentage of its predicted value), exercise duration, respiratory exchange ratio, peak work
rate, heart rate, O2 pulse, end-tidal carbon dioxide pressure (PetCO2), PetO2, and -if blood gas samples are
obtained-dead space to tidal volume ratio.Moreover,wewill discuss the physiological and clinical value of anaerobic
threshold, respiratory compensation point, ventilation vs. VCO2 and VO2 vs. work relationships. Finally, attention
will be dedicated to exercise-induced periodic breathing. We will also discuss when and why CPET
should be integrated with other measurements in the so-called complex CPET. Specifically: a) when and how
to use a complex non-invasive CPET, which integrates CPET measurementswith non-invasive cardiac output determination, working muscle near-infrared spectroscopy, transthoracic echocardiography, thoracic ultrasound,
and lung diffusion analysis; b) when and how to use a complex minimally invasive CPET, in which CPET is combined with esophageal balloon recordings or with serial arterial blood sampling for blood gas analysis; c) when
and how to use a complex invasive CPET, which usually implies the presence of a Swan Ganz catheter in the pulmonary artery and an arterial line.

Carli F, Minnella E

Minerva Anestesiol. 2017 Feb;83(2):214-218. doi: 10.23736/S0375-9393.16.11564-0.
Epub 2016 Oct 6.

Functional capacity has been shown to be a major determinant of surgical outcome
since it is related to postoperative complications, activity and daily function,
level of independence and quality of life. Anesthesiologists as “perioperative
physicians”, can identify those scoring systems that assess functional capacity,
whether from the basic physical history and walk test to the most complex such as
cardiopulmonary exercise testing, and formulate intraoperative and postoperative
interventions (rehabilitation) to minimize the impact of surgery on the recovery
process. Nevertheless, the preoperative period can be used as an opportune time
to increase functional reserve in anticipation of surgery, thus enabling the
patient to better withstand the metabolic cost of surgical stress
(prehabilitation). There is a compelling evidence that prehabilitation programs,
including physical exercise, nutritional optimization and relaxation strategies,
can enhance preoperative physiological reserve, however further studies are
needed to identify the most appropriate protocols for those patients at risk, and
assess the impact of such programs on clinically meaningful surgical outcomes.

Patel N; Powell AG; Wheat JR; Brown C; Appadurai IR; Davies RG; Bailey DM; Lewis WG;

Physiological Reports [Physiol Rep] 2019 Jul; Vol. 7 (14), pp. e14174.

Surgery for radical treatment of esophageal cancer (EC) carries significant inherent risk. The objective identification of patients who are at high risk of complications is of importance. In this study the prognostic value of cardiopulmonary fitness variables (CPF) derived from cardiopulmonary exercise testing (CPET) was assessed in patients undergoing potentially curative surgery for EC within an enhanced recovery program. OC patients underwent preoperative CPET using automated breath-by-breath respiratory gas analysis, with measurements taken during a ramped exercise test on a bicycle. The prognostic value of [Formula: see text] , Anaerobic Threshold (AT) and VE/VCO2 derived from CPET were studied in relation to post-operative morbidity, which was collected prospectively, and overall survival. Consecutive 120 patients were included for analysis (median age 65 years, 100 male, 75 neoadjuvant therapy). Median AT in the cohort developing major morbidity (Clavien-Dindo classification >2) was 10.4 mL/kg/min compared with 11.3 mL/kg/min with no major morbidity (P = 0.048). Median [Formula: see text] in the cohort developing major morbidity was 17.0 mL/kg/min compared with 18.7 mL/kg/min in the cohort (P = 0.009). [Formula: see text] optimum cut-off was 17.0 mL/kg/min (sensitivity 70%, specificity 53%) and for AT was 10.5 mL/kg/min (sensitivity 60%, specificity 44%). Multivariable analysis revealed [Formula: see text] to be the only independent factor to predict major morbidity (OR 0.85, 95% CI 0.75-0.97, P = 0.018). Cumulative survival was associated with operative morbidity severity (χ2 = 4.892, df = 1, P = 0.027). These results indicate that [Formula: see text] as derived from CPET is a significant predictor of major morbidity after oesophagectomy highlighting the physiological importance of cardiopulmonary fitness.

Singh I; Rahaghi FN; Naeije R; Oliveira RKF; Vanderpool RR; Waxman AB; Systrom DM;

Pulmonary Circulation [Pulm Circ] 2019 Jul-Sep; Vol. 9 (3), pp. 2045894019862435.

Despite recent advances, the prognosis of pulmonary hypertension (PH) remains poor. While the initial insult in PH implicates the pulmonary vasculature, the functional state, exercise capacity, and survival of such patients are closely linked to right ventricular (RV) function. In the current study, we sought to investigate the effects of maximum incremental exercise on the matching of RV contractility and afterload (i.e. right ventricular-pulmonary arterial [RV-PA] coupling) in patients with exercise PH (ePH) and pulmonary arterial hypertension (PAH). End-systolic elastance (Ees), pulmonary arterial elastance (Ea), and RV-PA coupling (Ees/Ea) were determined using single-beat pressure-volume loop analysis in 40 patients that underwent maximum invasive cardiopulmonary exercise testing. Eleven patients had ePH, nine had PAH, and 20 were age-matched controls. During exercise, the impaired exertional contractile reserve in PAH was associated with blunted stroke volume index (SVI) augmentation and reduced peak oxygen consumption (peak VO2 %predicted). Compared to PAH, ePH demonstrated increased RV contractility in response to increasing RV afterload during exercise; however, this was insufficient and resulted in reduced peak RV-PA coupling. The dynamic RV-PA uncoupling in ePH was associated with similarly blunted SVI augmentation and peak VO2 as PAH. In conclusion, dynamic rest-to-peak exercise RV-PA uncoupling during maximum exercise blunts SV increase and reduces exercise capacity in exercise PH and PAH. In ePH, the insufficient increase in RV contractility to compensate for increasing RV afterload during maximum exercise leads to deterioration of RV-PA coupling. These data provide evidence that even in the early stages of PH, RV function is compromised.

Zanini M; Nery RM;de Lima JB;Buhler RP;da Silveira AD; Stein R

Journal Of Cardiopulmonary Rehabilitation And Prevention [J Cardiopulm Rehabil Prev] 2019 Jul 22. Date of Electronic Publication: 2019 Jul 22.

Purpose: Patients undergoing coronary artery bypass graft (CABG) surgery typically experience loss of cardiopulmonary capacity in the post-operative period. The purpose of this study was to evaluate the effects of different rehabilitation protocols used in inpatient cardiac rehabilitation on functional capacity and pulmonary function in patient status post-CABG surgery.
Methods: This was a single-blind randomized controlled trial. The primary endpoint of functional capacity and secondary endpoints of lung capacity and respiratory muscle function were assessed in patients scheduled to undergo CABG. After surgery, 40 patients were randomly assigned across 1 of 4 inpatient cardiac rehabilitation groups: G1, inspiratory muscle training, active upper limb and lower limb exercise training, and early ambulation; G2, same protocol as G1 without inspiratory muscle training; G3, inspiratory muscle training alone; and G4, control. All groups received chest physical therapy and expiratory positive airway pressure. Patients were reassessed on post-operative day 6 and post-discharge day 30 (including cardiopulmonary exercise testing).
Results: The 6-min walk distance on post-operative day 6 was significantly higher in groups that included exercise training (G1 and G2), remaining higher at 30 d post-discharge (P < .001 between groups). Peak oxygen uptake on day 30 was also higher in G1 and G2 (P = .005). All groups achieved similar recovery of lung function.
Conclusion: Protocols G1 and G2, which included a systematic plan for early ambulation and upper and lower limb exercise, attenuated fitness losses while in the hospital and significantly enhanced recovery 1 mo after CABG.

Palau P; Domínguez E; Núñez J;

ESC Heart Failure [ESC Heart Fail] 2019 Jul 19. Date of Electronic Publication: 2019 Jul 19.

Women represent nearly half of the adult heart failure (HF) population and they remain underrepresented in HF studies. We aimed to evaluate the evidence about peak oxygen uptake (peak VO2 ) for clinical stratification in women with HF. This narrative review summarizes (i) the evidence endorsing the value of cardiopulmonary exercise testing for clinical stratification and phenotyping HF population; (ii) the determinants of a person’s functional aerobic capacity to understand predicted values for patients with chronic HF; and (iii) sex differences on peak VO2 data in different forms of HF. Lastly, based on existing data in patients with HF, we provide a perspective on how to improve existing gaps about the utility of peak VO2 in clinical stratification in women. Peak VO2 provides prognosis information in patients with HF; however, its use has been limited for a reduced number of patients excluding women, elderly, and HF patients with preserved ejection fraction. Further studies will help to fill the wide gender gap about the utility of cardiopulmonary exercise testing in the risk assessment and management in women with HF.

Kim BJ; Kim Y; Oh J; Jang J; Kang SM.

Yonsei Medical Journal. 60(6):547-553, 2019 Jun.
VI 1

PURPOSE: Clinical use of cardiopulmonary exercise tests (CPETs) is
increasing in elderly patients with cardiovascular (CV) diseases. However,
data on Korean populations are limited. In this study, we aimed to examine
the characteristics and safety of CPET in an elderly Korean population
with CV disease.

MATERIALS AND METHODS: We retrospectively analyzed records of 1485
patients (older than 65 years in age, with various underlying CV diseases)
who underwent CPET. All CPET was performed using the modified Bruce ramp
protocol.

RESULTS: The mean age of patients was 71.6+/-4.7 years with 63.9% being
men, 567 patients aged 60-65 years, 818 patients aged 70-79 years, and 100
patients aged 80-89 years. The mean respiratory exchange ratio was
1.09+/-0.14. During CPET, three adverse cardiovascular events occurred
(total 0.20%), all ventricular tachycardia. All subjects showed an average
exercise capacity of 21.3+/-5.5 mL/kg/min at peak VO2 and 6.1+/-1.6
metabolic equivalents of task, and men showed better exercise capacity
than women on most CEPT parameters. A significant difference was seen in
peak oxygen uptake according to age group (65-69 years, 22.9+/-5.8; 70-79
years, 20.7+/-5.1; 80-89 years, 17.0+/-4.5 mL/kg/min, p<0.001). The most
common causes for CPET termination were dyspnea (64.8%) and leg pain
(24.3%), with higher incidence of leg pain in octogenarians compared to
other age groups (65-69 years, 22.4%; 70-79 years, 24.6%; 80-89 years,
32.0%, p<0.001).

CONCLUSION: CPET was relatively a safe and useful modality to assess
exercise capacity, even in an elderly Korean population with underlying CV
diseases.

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

Mayo Clinic Proceedings [Mayo Clin Proc] 2019 Jul 11. Date of Electronic Publication: 2019 Jul 11.

Objective: To assess the influence of changes in cardiorespiratory fitness (CRF) after exercise training on mortality risk in a cohort of self-referred, apparently healthy adults.
Patients and Methods: A total of 683 participants (404 men, 279 women; mean age: 42.7±11.0 y) underwent two maximal cardiopulmonary exercise tests (CPX) between March 20, 1970, and December 11, 2012, to assess CRF at baseline (CPX1) and post-exercise training (CPX2). Participants were followed for an average of 29.8±10.7 years after their CPX2. Cox proportional hazards models were performed to determine the relationship of CRF change with mortality, with change in CRF as a continuous variable, as well as a categorical variable. A Wald chi-square test was used to compare the coefficients estimating the relationship of peak oxygen consumption (VO2peak) at CPX1 with VO2peak measured at CPX2 with time until death for all-cause mortality.
Results: During the follow-up period there were 180 deaths. When assessed independently, there were 20% (95% CI, 10-49%) and 38% (95% CI, 7-66%) lower mortality risks per 1 metabolic equivalent improvement in CRF (P<.01) in men and women, respectively, after multivariable adjustment. Those that remained unfit had ∼2-fold higher risk for all-cause mortality compared with those that remained fit and CRF at CPX2 was a stronger predictor of all-cause mortality than at CPX1 (P=.02).
Conclusion: Improving CRF through exercise training lowers mortality risk. Clinicians should encourage individuals to participate in exercise training to improve CRF to lower risk of mortality.