Simpson SJ; Champion Z; Hall GL; French N; Reynolds V;

The Journal Of Pediatrics [J Pediatr] 2019 Aug 08. Date of Electronic Publication: 2019 Aug 08.

Objective: To evaluate the role of upper airway dysfunction, indicated by altered vocal quality (dysphonia), on the respiratory symptoms of children surviving very preterm birth.
Study Design: Children born <32 weeks of gestation participated in 2 separate assessments during midchildhood. The first visit assessed voice quality by a subjective evaluation using the Consensus Auditory-Perceptual Evaluation of Voice and a computerized analysis of the properties of the voice via the Acoustic Voice Quality Index. The second assessment recorded parentally reported respiratory symptoms and measures of lung function, including spirometry, lung volumes, oscillatory mechanics, and a cardiopulmonary exercise test.
Results: Preterm children (n = 35; median gestation 24.3 weeks) underwent paired voice and lung assessments at approximately 11 years of age. Preterm children with dysphonia (n = 25) reported significantly more respiratory symptoms than those with normal voices (n = 10) including wheeze (92% vs 40%; P = .001) and asthma diagnosed by a physician (60% vs 10%; P = .007). Lung function outcomes were generally not different between the dysphonic group and the group with normal voice (P > .05), except for the oscillatory mechanics measures, which were all at least 0.5 z score lower in the dysphonic group (Xrs8 mean difference = -0.91 z scores, P = .003; fres = 1.06 z scores, P = .019; AX = -0.87 z scores, P = .010; Rrs8 = 0.63 z scores, P = .068).
Conclusions: The upper airway may play a role in the respiratory symptoms experienced by some very preterm children and should be considered by clinicians, especially when symptoms are in the presence of normal lung function and are refractory to treatment.

Nemoto S; Kasahara Y; Izawa KP; Watanabe S; Yoshizawa K; Takeichi N; Kamiya K; Suzuki N; Omiya K; Matsunaga A; Akashi YJ;

International Journal Of Environmental Research And Public Health [Int J Environ Res Public Health] 2019 Aug 08; Vol. 16 (16). Date of Electronic Publication: 2019 Aug 08.

A simplified substitute for heart rate (HR) at the anaerobic threshold (AT), i.e., resting HR plus 30 beats per minute or a percentage of predicted maximum HR, is used as a way to determine exercise intensity without cardiopulmonary exercise testing (CPX) data. However, difficulties arise when using this method in subacute myocardial infarction (MI) patients undergoing beta-blocker therapy. This study compared the effects of αβ-blocker and β1-blocker treatment to clarify how different beta blockers affect HR response during incremental exercise. MI patients were divided into αβ-blocker (n = 67), β1-blocker (n = 17), and no-β-blocker (n = 47) groups. All patients underwent CPX one month after MI onset. The metabolic chronotropic relationship (MCR) was calculated as an indicator of HR response from the ratio of estimated HR to measured HR at AT (MCR-AT) and peak exercise (MCR-peak). MCR-AT and MCR-peak were significantly higher in the αβ-blocker group than in the β1-blocker group (p < 0.001, respectively). Multiple regression analysis revealed that β1-blocker but not αβ-blocker treatment significantly predicted lower MCR-AT and MCR-peak (β = -0.432, p < 0.001; β = -0.473, p < 0.001, respectively). Based on these results, when using the simplified method, exercise intensity should be prescribed according to the type of beta blocker used.

Forton K; Motoji Y; Pezzuto B; Caravita S; Delbaere A; Naeije R;Faoro V;

Human Reproduction (Oxford, England) [Hum Reprod] 2019 Aug 13. Date of Electronic Publication: 2019 Aug

13.Study Question: What is the functional relevance of decreased pulmonary vascular distensibility in adolescents conceived by IVF?
Summary Answer: Children born by IVF have a slight decrease in pulmonary vascular distensibility observed during normoxic exercise that is not associated with altered right ventricular function and aerobic exercise capacity.
What Is Known Already: General vascular dysfunction and increased hypoxic pulmonary hypertension have been reported in ART children as compared to controls. Pulmonary hypertension or decreased pulmonary vascular distensibility may affect right ventricular function and thereby possibly limit maximal cardiac output and aerobic exercise capacity.
Study Design, Size, Duration: This prospective case-control study enrolled 15 apparently healthy adolescents conceived by IVF/ICSI after fresh embryo transfer paired in a 2 to 1 ratio to 30 naturally conceived adolescents between March 2015 and May 2018.
Participants/materials, Setting, Methods: Fifteen IVF/ICSI adolescents and 30 controls from singleton gestations matched by age, gender, weight, height and physical activity underwent exercise echocardiography, lung diffusion capacity measurements and a cycloergometer cardiopulmonary exercise test. A pulmonary vascular distensibility coefficient α was determined from the pulmonary arterial pressure (PAP) versus cardiac output (Q) relationships. Pulmonary capillary volume (Vc) was calculated from single breath nitric oxide and carbon monoxide lung diffusion capacity measurements (DLCO and DLNO) at rest and during exercise (100 W). Eight of the IVF subjects and eight controls underwent a 30 min hypoxic challenge at rest with a fraction of inspired oxygen of 0.12 to assess hypoxic pulmonary vasoconstriction.
Main Results and the Role Of Chance: In normoxia, oxygen uptake (VO2), blood pressure, DLCO, DLNO, echocardiographic indices of right ventricular function, Q and PAP at rest and during exercise were similar in both groups. However, IVF children had a lower pulmonary vascular distensibility coefficient α (1.2 ± 0.3 versus 1.5 ± 0.3%/mmHg, P = 0.02) and a blunted exercise-induced increase in Vc (24 versus 32%, P < 0.05). Hypoxic-induced increase in pulmonary vascular resistance in eight IVF subjects versus eight controls was similar.
Limitations, Reasons For Caution: The IVF cohort was small, and thus type I or II errors could have occurred in spite of careful matching of each case with two controls. ART evolved over the years, so that it is not certain that the presently reported subtle changes will be reproducible in the future. As the study was limited to singletons born after fresh embryo transfers, our observations cannot be extrapolated to singletons born after frozen embryo transfer.
Wider Implications Of the Findings: The present study suggests that adolescents conceived by IVF have preserved right ventricular function and aerobic exercise capacity despite a slight alteration in pulmonary vascular distensibility as assessed by two entirely different methods, i.e. exercise echocardiography and lung diffusing capacity measurements. However, the long-term prognostic relevance of this slight decrease in pulmonary vascular distensibility needs to be evaluated in prospective large scale and long-term outcome studies.

Santana S; Gidding SS; Xie S; Jiang T; Kharouf R; Robinson BW;

Pediatric Cardiology [Pediatr Cardiol] 2019 Aug 07. Date of Electronic Publication: 2019 Aug 07.

Previous pediatric exercise test criteria for aortic stenosis severity were based on cardiac catheterization assessment, whereas current criteria are based on echocardiographic valve gradients. We sought to correlate exercise test criteria with echocardiographic assessment of severity. We report 65 studies, 51 patients (mean age of 13 ± 4 years; 75% males), with aortic stenosis (AS) who had a maximal exercise test between 2005 and 2016. We defined three groups based on resting mean Doppler gradient across their aortic valve: severe AS (n = 10; gradient of ≥ 40 mmHg), moderate AS (n = 20; gradient 25-39 mmHg), and mild AS (n = 35; gradient ≤ 24 mmHg). We studied symptoms (chest pain) during exercise, resting electrocardiogram changes (left ventricular hypertrophy [LVH]), complex arrhythmias during exercise, change in exercise systolic blood pressure (SBP; delta SBP = peak SBP-resting SBP), exercise duration, work, echocardiogram parameters (LVH), and ST-T wave changes with exercise. Additionally, we compared work and delta SBP during exercise with 117 control males and females without heart disease. Severe AS patients have statistically significant differences when compared with mild AS in ST-T wave depression during exercise, LVH on resting electrocardiogram, and echocardiogram. There was a significant difference in delta SBP between severe AS and normal controls (delta SBP 21.6 vs. 46.2 mmHg), and between moderate AS and normal controls (delta SBP 32 vs. 46.2 mmHg). There were no significant complications during maximal exercise testing. Children with echocardiographic severe and moderate AS have exercise testing abnormalities. Exercise test criteria for severity of AS were validated for echocardiographic criteria for AS severity.

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.