Wallen MP; Woodward AJ; Hall A; Skinner TL; Coombes JS; Macdonald GA;

Transplantation [Transplantation] 2018 Jul 13. Date of Electronic Publication: 2018 Jul 13.

Background: Patients with advanced liver disease are at increased risk of infection and other complications. A significant proportion of patients also have poor fitness and low muscle mass. The primary aim of this study was to investigate if cardiorespiratory fitness and body composition are risk factors for sepsis and other complications of advanced liver disease.
Methods: Patients being listed for liver transplantation underwent cardiopulmonary exercise testing to determine ventilatory threshold (VT). Computed tomography was used to measure skeletal muscle and subcutaneous and visceral adipose tissue indexes. All unplanned hospital admissions, deaths or delistings prior to transplantation were recorded.
Results: Eighty-two patients [aged 55.1 (50.6-59.4) years, median (interquartile range); male 87%] achieved a median VT of 11.7 (9.7-13.4) mL[BULLET OPERATOR]kg[BULLET OPERATOR]min. Their median MELD-Na score was 18 (14-22); and 37 had hepatocellular carcinoma. There were 50 admissions in 31 patients; with 16 admissions for sepsis in 13 patients. Patients with sepsis had a significantly lower VT [sepsis 9.5 (7.8-11.9), no sepsis 11.8 (10.5-13.8) mL[BULLET OPERATOR]kg[BULLET OPERATOR]min; P=0.003]. No body composition variables correlated with sepsis, nor were there any significant associations between VT and unplanned admissions for other indications. Multivariate logistic regression demonstrated that VT was independently associated with a diagnosis of sepsis (P=0.03). Poisson regression revealed that VT was a significant predictor for the number of septic episodes (P=0.02); independent of age, MELD-Na score, hepatocellular carcinoma diagnosis, presence of ascites, and beta-blocker use.
Conclusion: Poor cardiorespiratory fitness is an independent risk factor for the development of sepsis in advanced liver disease.

Weberruss H, Maucher J, Oberhoffer R, Müller J.

Eur J Appl Physiol. 2018 Jan;118(1):205-211. doi: 10.1007/s00421-017-3762-2. Epub
2017 Nov 15.

OBJECTIVE: The body’s adaptation to physical exercise is modulated by sympathetic
and parasympathetic (vagal) branches of the autonomic nervous system (ANS). Heart
rate variability (HRV), the beat-to-beat variation of the heart, is a proxy
measure for ANS activity, whereas blood pressure (BP) is an indicator for
cardiovascular function. Impaired vagal activity and lower BP is already
described after exercise. However, inconsistent results exist about how long
vagal recovery takes and how long post-exercise hypotension persists. Therefore,
the aim of this study was to assess HRV and BP 1 h after maximal cardiopulmonary
exercise testing (CPET).
PATIENTS AND METHODS: HRV (Polar RS800CX), peripheral and central BP
(Mobil-O-Graph®) were prospectively studied in 107 healthy volunteers (47 female,
median age 29.0 years) in supine position, before and 60 min after maximal CPET.
RESULTS: One hour after terminating CPET measures of HRV were still impaired and
post-exercise BP was significantly reduced suggesting an improved vascular
function compared to pre levels. HRV parameters post-exercise were 34.7% (RMSSD),
67.2% (pNN50), 57.2% (HF), and 42.7% (LF) lower compared to pre-exercise levels
(for all p < 0.001). Median reduction in BP was 5 mmHg for systolic BP
(p < 0.001), and 4 mmHg for diastolic BP (p = 0.016) and central systolic
post-exercise (p = 0.005).
CONCLUSIONS: One hour after terminating strenuous exercise, autonomic nervous
regulation seems to be postponed which is reflected in reduced HRV, whereas the
early recovery of the vasculature, post-exercise hypotension, is still preserved
over the recovery period of 1 h.

Li M, Lu Y, Fang C, Zhang X

Echocardiography. 2017 Nov;34(11):1640-1648. doi: 10.1111/echo.13675. Epub 2017
Sep 19.

PURPOSE: Heart failure (HF) is a multifactorial entity that combines derangements
in both systolic and diastolic function. The relationship between systolic and
diastolic function and exercise capacity is not fully understood. We sought to
determine the mechanisms linking cardiac function and exercise tolerance in
patients with HF.
METHODS: One hundred fifty-six subjects with different cardiac function levels
were included in the study. Subjects’ 2D echocardiographic, 3D speckle tracking
echocardiographic, and cardiopulmonary exercise testing (CPET) data were
collected.
RESULT: The amount of untwisting at 25% of the untwist duration (25%Untwist) and
global longitudinal peak systolic strain (GLS) showed the best positive
correlations with peak oxygen uptake (peakVO2 ) (r = .41; P < .001 and r = .32;
P < .001, respectively), while the left ventricular ejection fraction (EF) was
weakly correlated with peakVO2 . The 25%Untwist value was negatively correlated
with the carbon dioxide equivalent slope (VE/VCO2 ) (r = -.49; P < .001). Both
E/e and the left atrium volume index (LA index) exhibited good positive
correlations with VE/VCO2 (r = .39; P < .01 and r = .32; P < .001). In the
multiple regression analysis, the best predictive model for the peakVO2 included
the 25%Untwist, GLS, and E/e, explained 64% of the variation in peakVO2 , with
25%Untwist explaining 17.6% of the variation. Including EF in the model explained
only 3.1% of the variation in peakVO2 . In a multivariable model for VE/VCO2 ,
25%Untwist was the strongest independent predictor, explaining 23% of the
variance in VE/VCO2 .
CONCLUSION: Left ventricular early diastolic function is a modest independent
predictor of aerobic exercise capacity. The 25%Untwist value is a good indicator
of cardiac diastolic function.

S.W. Grant, G.L. Hickey, N.A. Wisely, E.D. Carlson, R.A. Hartley, A.C. Pichel, D. Atkinson, C.N. McCollum

Wilson RJT.

Br J Anaesth. 2018;120(6):1145-1146.

Editorial

Rose GA, Davies RG, Davison GW, et al.

Br J Anaesth. 2018;120(6):1187-1194.

BACKGROUND: Cardiorespiratory fitness can inform patient care, although to what extent natural variation in CRF influences clinical practice remains to be established. We calculated natural variation for cardiopulmonary exercise test (CPET) metrics, which may have implications for fitness stratification.
METHODS: In a two-armed experiment, critical difference comprising analytical imprecision and biological variation was calculated for cardiorespiratory fitness and thus defined the magnitude of change required to claim a clinically meaningful change. This metric was retrospectively applied to 213 patients scheduled for colorectal surgery. These patients underwent CPET and the potential for misclassification of fitness was calculated. We created a model with boundaries inclusive of natural variation [critical difference applied to oxygen uptake at anaerobic threshold (V O2-AT): 11 ml O2 kg(-1) min(-1), peak oxygen uptake (V O2 peak): 16 ml O2 kg(-1) min(-1), and ventilatory equivalent for carbon dioxide at AT (VE/VCO2-AT): 36].
RESULTS: The critical difference for V O2-AT, V O2 peak, and V E/V CO2-AT was 19%, 13%, and 10%, respectively, resulting in false negative and false positive rates of up to 28% and 32% for unfit patients. Our model identified boundaries for unfit and fit patients: AT <9.2 and >/=13.6 ml O2 kg(-1) min(-1), V O2 peak <14.2 and >/=18.3 ml kg(-1) min(-1), V E/V CO2-AT >/=40.1 and <32.7, between which an area of indeterminate-fitness was established. With natural variation considered, up to 60% of patients presented with indeterminate-fitness.
CONCLUSIONS: These findings support a reappraisal of current clinical interpretation of cardiorespiratory fitness highlighting the potential for incorrect fitness stratification when natural variation is not accounted for.

Godinas L, Sattler C, Lau EM, Jaïs X, Taniguchi Y, Jevnikar M,
Weatherald J, Sitbon O, Savale L, Montani D, Simonneau G, Humbert
M, Laveneziana P, Garcia G.

J Heart Lung Transplant. 2017 Nov;36(11):1234-1242. doi:
10.1016/j.healun.2017.05.024. Epub 2017 May 22.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is frequently used for the
evaluation of patients with pulmonary hypertension (PH). Non-operable distal
chronic thromboembolic pulmonary hypertension (CTEPH) represents a unique
subgroup of PH where microvascular disease resembling pulmonary arterial
hypertension (PAH) may predominate and efficacious medical therapy is now
available. However, little is known regarding the detailed CPET profile of
patients with distal CTEPH, and whether ventilation and gas exchange responses
are different from PAH.
METHODS: Forty-nine consecutive patients with non-operable distal CTEPH according
to multidisciplinary team assessment and 45 PAH patients underwent CPET and right
heart catheterization. Patients were followed up for a median of 3.2 years
(interquartile range: 1.8 to 4.4).
RESULTS: Pulmonary hemodynamics were similar in distal CTEPH and PAH groups, but
patients with distal CTEPH achieved a lower percent predicted peak oxygen
consumption (59 ± 13% vs 66 ± 14%, p < 0.05). At peak exercise, higher
physiologic dead-space fraction (VD/VT) (0.45 ± 0.07 vs 0.35 ± 0.07, p < 0.0001)
and higher arterial-to-end-tidal carbon dioxide gradient (9 ± 3 vs 5 ± 3 mm Hg, p
< 0.0001) were observed in distal CTEPH compared with PAH. Ventilatory
efficiency, expressed as VE/VCO2 slope, was also more impaired in distal CTEPH
(52.2 ± 10.1 vs 43.8 ± 8.4 liters/min, p < 0.0001). In the distal CTEPH group
only, higher VD/VT was associated with lower peak oxygen consumption (r = -0.46,
p = 0.003) and worse survival.
CONCLUSIONS: Compared with PAH, a distinct pattern of response to exercise was
observed in distal CTEPH, characterized by increased dead-space ventilation that
resulted in worse ventilatory efficiency and greater impairment of exercise
capacity. In distal CTEPH, dead-space ventilation correlated with exercise
capacity and was associated with survival.

Sato T, Yoshihisa A, Kanno Y, Suzuki S, Yamaki T, Sugimoto K,
Kunii H, Nakazato K, Suzuki H, Saitoh SI, Ishida T, Takeishi Y

Eur J Prev Cardiol. 2017 Dec;24(18):1979-1987.

Aims
We aimed to determine the differences of impact of cardiopulmonary exercise
testing (CPX) parameters on prognosis of heart failure with reduced left
ventricular ejection fraction (HFrEF), preserved ejection fraction (HFpEF) and
mid-range ejection fraction (HFmrEF).
Methods
We compared clinical
characteristics and CPX parameters among the three groups, and the value of each
CPX parameter to predict adverse cardiac events (cardiac deaths and
re-hospitalizations for heart failure), cardiac deaths and all-cause deaths.
Results
Of 1190 patients, 41.9% had HFrEF, 36.8% had HFpEF and 21.3% had HFmrEF.
The patients in HFrEF group had higher rates of adverse cardiac events, cardiac
death and all-cause death than those of HFpEF and HFmrEF groups. In HFrEF, the
independent predictors of adverse cardiac events were peak oxygen consumption and
oxygen uptake efficiency slope, predictors of cardiac death were peak oxygen
consumption and oxygen uptake efficiency slope, and the predictor of all-cause
death was peak oxygen consumption. In HFpEF, the predictor of adverse cardiac
events was peak oxygen consumption, predictors of cardiac deaths and all-cause
deaths were peak oxygen consumption and exertional oscillatory ventilation. In
HFmrEF, predictors of adverse cardiac events were peak oxygen consumption and
oxygen uptake efficiency slope, and the predictor of cardiac deaths and all-cause
deaths was peak oxygen consumption.
Conclusion
Peak oxygen consumption is the
strong predictor for adverse events in all groups. Oxygen uptake efficiency slope
predicts adverse prognosis in HFrEF, but not in HFpEF. In contrast, exertional
oscillatory ventilation is the predictor only in HFpEF. Thus, different CPX
parameters may be able to differentially predict prognosis in HFrEF and HFpEF.
Those for predicting prognosis in HFmrEF may be intermediate between HFrEF and
HFpEF.