Moroni F; Many centres in USA and Italy
Golino M; Carbone S; Trankle C; Del Buono MG; Talasaz A; Arena
R; Canada JM; Biondi-Zoccai G; Van Tassel B; Abbate A

ESC heart failure. 10(5):3199-3202, 2023 Oct.

AIMS: Interleukin-1 (IL-1) blockade may improve exercise capacity in
patients with heart failure (HF) patients. The extent of the improvement
and its persistence beyond discontinuation of IL-1 blockade is unknown.
METHODS AND RESULTS: The primary objective was to determine changes in
cardiorespiratory fitness and cardiac function on-treatment with IL-1
blocker, anakinra, and off-treatment, after treatment cessation. We
performed cardiopulmonary exercise testing, Doppler echocardiography, and
biomarkers in 73 patients with HF, 37 (51%) females, 52 (71%)
Black-African-American, before and after treatment with anakinra 100 mg
daily. In a subset of 46 patients, testing was also repeated after
treatment cessation. Quality of life was assessed in each patient using
standardized questionnaires. Data are presented as median and
interquartile range. Treatment with anakinra for 4 [2-12] weeks was
associated with a significant improvement in high-sensitivity C-reactive
protein (from 6.2 [3.3-15.4] to 1.4 [0.8-3.4] mg/L, P < 0.001), peak
oxygen consumption (VO2peak , from 13.9 [11.6-16.6] to 15.2 [12.9-17.4]
mL/kg/min, P < 0.001). Ventilatory efficiency, exercise time,
Doppler-derived signs and biomarkers of elevated intracardiac pressures,
and quality-of-life measures also improved with anakinra. In the 46
patients in whom off-treatment data were available 12 [4-12] weeks later,
many of the favourable changes seen with anakinra were largely reversed
(from 1.5 [1.0-3.4] to 5.9 [1.8-13.1], P = 0.001 for C-reactive protein,
and from 16.2 [14.0-18.4] to 14.9 [11.5-17.8] mL/kg/min, P = 0.017, for
VO2peak ).
CONCLUSIONS: These data validate IL-1 as an active and dynamic modulator
of cardiac function and cardiorespiratory fitness in HF.

K. Kristenson, Linköping University, Sweden
E. Gerring, B. Bjornsson, P. Sandstrom and K. Hedman

Physiol Rep 2024 Vol. 12 Issue 1 Pages e15904

This pilot study aimed to evaluate if peak VO(2) and ventilatory efficiency in combination would improve preoperative risk stratification beyond only relying on peak VO(2) . This was a single-center retrospective cohort study including all patients who underwent cardiopulmonary exercise testing (CPET) as part of preoperative risk evaluation before major upper abdominal surgery during years 2008-2021. The primary outcome was any major cardiopulmonary complication during hospitalization. Forty-nine patients had a preoperative CPET before decision to pursue to surgery (cancer in esophagus [n = 18], stomach [6], pancreas [16], or liver [9]). Twenty-five were selected for operation. Patients who suffered any major cardiopulmonary complication had lower ventilatory efficiency (i.e., higher VE/VCO(2) slope, 37.3 vs. 29.7, p = 0.031) compared to those without complications. In patients with a low aerobic capacity (i.e., peak VO(2) < 20 mL/kg/min) and a VE/VCO(2) slope >/= 39, 80% developed a major cardiopulmonary complication. In this pilot study of patients with preoperative CPET before major upper abdominal surgery, patients who experienced a major cardiopulmonary complication had significantly lower ventilatory efficiency compared to those who did not. A low aerobic capacity in combination with low ventilatory efficiency was associated with a very high risk (80%) of having a major cardiopulmonary complication.

de Souza JAF; Physiotherapy Dept, Federal University of Pernambuco (UFPE) and Federal University of Sao Carlos (UFSCAR)Brazil.
Catai AM; Araújo BTS; Barros AEVR; de Aguiar MIR; Campos SL; de Andrade AD; Brandão DC;

Heart & lung : the journal of critical care [Heart Lung] 2023 Dec 12.
Date of Electronic Publication: 2023 Dec 12.

Background: Endothelial dysfunction and peak oxygen uptake (VO _2peak ) are also predictors of increased risk of cardiovascular events in heart transplantation (HTx) recipients. The preservation of endothelial function may contribute to exercise tolerance.
Objective: To investigate the correlation between peripheral endothelial function and exercise tolerance through VO _2peak and ventilation to carbon dioxide production slope (VE / VCO _{2 slope} ) in HTx recipients.
Methods: A pilot cross-sectional study was conducted with adult individuals aged 18-65 years, HTx ≥ six months after surgery, who had a stable medical condition and no changes over the last three months of immunosuppressive treatment. The patients underwent an assessment of endothelial function through PAT (EndoPAT-2000®) and performed a cardiopulmonary exercise test (CPET).
Results: A total of 41% of the studied population presented endothelial dysfunction. The individuals were divided into two groups: the endothelial dysfunction (GED; n=9) group and the normal endothelial function (GNEF; n=13) group according to the logarithm of the reactive hyperemia index (LnRHI). There was a positive and moderate correlation between the LnRHI and VO _{2 peak} (r=0.659, p=0.013) and a negative and moderate correlation between the LnRHI and VE/VCO _{2 slope} (r= -0.686, p= 0.009) in the GNEF. However, no significant correlations were found in the GED.
Conclusion: The results showed that the preservation of peripheral endothelial function is significantly correlated with an increase in exercise tolerance in individuals after HTx. These findings bring important considerations for cardiovascular risk prevention and emphasize that therapeutic strategies with physical training programs must be implemented early.

Franssen RFW;  Maastricht University, and other centres in the Netherlands.
Berkel AEM; Ten Cate DWG; van der Palen J; Vogelaar FJ; Slooter G; Klaase JM; Janssen-Heijnen Bongers BC

Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 9808285 Publication Model: Electronic Cited Medium:
Internet ISSN: 1435-2451 (Electronic) Linking ISSN: 14352443 NLM ISO Abbreviation: Langenbecks Arch Surg Subsets: MEDLINE

Purpose: This study aimed to investigate the association of effort-independent variables derived from the preoperative cardiopulmonary exercise test (CPET) with 30-day postoperative complications after elective colorectal surgery.
Methods: A multicenter (n=4) retrospective explorative study was performed using data of patients who completed a preoperative CPET and underwent elective colorectal surgery. The preoperative slope of the relation between minute ventilation and carbon dioxide production (VE/VCO ₂ -slope) and the oxygen uptake efficiency slope (OUES), as well as 30-day postoperative complications, were assessed. Multivariable logistic regression analyses and receiver operating characteristic (ROC) curves were used to investigate the prognostic value of the relationship between these preoperative CPET-derived effort-independent variables and postoperative complications.
Results: Data from 102 patients (60.1% males) with a median age of 72.0 (interquartile range 67.8-77.4) years were analyzed. Forty-four patients (43.1%) had one or more postoperative complications (of which 52.3% general and 77.3% surgical complications). Merely 10 (9.8%) patients had a general complication only. In multivariate analysis adjusted for surgical approach (open versus minimally invasive surgery), the VE/VCO ₂ -slope (odds ratio (OR) 1.08, confidence interval (CI) 1.02-1.16) and OUES (OR 0.94, CI 0.89-1.00) were statistically significant associated with the occurrence of 30-day postoperative complications.
Conclusion: The effort-independent VE/VCO ₂ -slope and OUES might be used to assist in future preoperative risk assessment and could especially be of added value in patients who are unable or unwilling to deliver a maximal cardiorespiratory effort. Future research should reveal the predictive value of these variables individually and/or in combination with other prognostic (CPET-derived) variables for postoperative complications.
Trial Registration Number: ClinicalTrials.gov NCT05331196.

Griffith GJ; Feinberg School of Medicine, Chicago, IL
Wang AP; Liem RI; Carr MR; Corson T; Ward K

Journal of Pediatrics. 264:113770, 2024 Jan.

OBJECTIVE: To develop reference values for cardiorespiratory fitness, as
quantified by peak oxygen uptake (VO2peak) and treadmill time, in patients
aged 6 through 18 years referred for cardiopulmonary exercise testing
(CPET).
STUDY DESIGN: We reviewed a clinical pediatric CPET database for fitness
data in children aged 6-18 years with no underlying heart disease. CPET
was obtained via the Bruce protocol utilizing objectively confirmed
maximal effort via respiratory exchange ratio. Fitness data (VO2peak and
treadmill test duration) were analyzed to determine age- and sex-specific
reference values for this pediatric cohort.
RESULTS: Data from 2025 pediatric CPETs (53.2% female) were included in
the analyses. VO2peak increased with age in males, but not females.
Treadmill test duration increased with age in both males and females.
Fitness was generally higher in males when compared with females in the
same age groups.
CONCLUSIONS: Our study provides extensive reference values for both
VO2peak and total treadmill test time via the Bruce protocol for a
pediatric population without known cardiac disease. Furthermore, the
inclusion of objectively confirmed maximal exercise effort increases
confidence in these findings compared with prior studies in this area.
Clinicians performing CPET in pediatric populations can utilize these
reference

Arbee-Kalidas N;  University of the Witwatersrand, Johannesburg, South Africa
Moutlana HJ; Moodley Y; Kebalepile MM; Motshabi Chakane P

PLoS ONE [Electronic Resource]. 18(12):e0295430, 2023

BACKGROUND: Exercise capacity should be determined in all patients
undergoing lung resection for lung cancer surgery and cardiopulmonary
exercise testing (CPET) remains the gold standard. The purpose of this
study was to investigate associations between preoperative CPET and
postoperative outcomes in patients undergoing lung resection surgery for
lung cancer through a review of the existing literature.
METHODS: A search was conducted on PubMed, Scopus, Cochrane Library and
CINAHL from inception until December 2022. Studies investigating
associations between preoperative CPET and postoperative outcomes were
included. Risk of bias was assessed using the QUIPS tool. A random effect
model meta-analysis was performed. I2 > 40% indicated a high level of
heterogeneity.
RESULTS: Thirty-seven studies were included with 6450 patients.
Twenty-eight studies had low risk of bias. [Formula: see text] peak is the
oxygen consumption at peak exercise and serves as a marker of
cardiopulmonary fitness. Higher estimates of [Formula: see text] peak,
measured and as a percentagege of predicted, showed significant
associations with a lower risk of mortality [MD: 3.66, 95% CI: 0.88; 6.43
and MD: 16.49, 95% CI: 6.92; 26.07] and fewer complications [MD: 2.06, 95%
CI: 1.12; 3.00 and MD: 9.82, 95% CI: 5.88; 13.76]. Using a previously
defined cutoff value of > 15mL/kg/min for [Formula: see text] peak, showed
evidence of decreased odds of mortality [OR: 0.55, 95% CI: 0.28-0.81] and
but not decreased odds of postoperative morbidity [OR: 0.82, 95% CI:
0.64-1.00]. There was no relationship between [Formula: see text] slope,
which depicts ventilatory efficiency, with mortality [MD: -9.60, 95% CI:
-27.74; 8.54] however, patients without postoperative complications had a
lower preoperative [Formula: see text] [MD: -2.36, 95% CI: -3.01; -1.71].
Exercise load and anaerobic threshold did not correlate with morbidity or
mortality. There was significant heterogeneity between studies.
CONCLUSIONS: Estimates of cardiopulmonary fitness as evidenced by higher
[Formula: see text] peak, measured and as a percentage of predicted, were
associated with decreased morbidity and mortality. A cutoff value of
[Formula: see text] peak > 15mL/kg/min was consistent with improved
survival but not with fewer complications. Ventilatory efficiency was
associated with decreased postoperative morbidity but not with improved
survival. The heterogeneity in literature could be remedied with large
scale, prospective, blinded, standardised research to improve preoperative
risk stratification in patients with lung cancer scheduled for lung
resection surgery.

Behnia M; Sietsema KE;  Harbor-UCLA Medical Center, Torrance, CA, USA.

International Journal of Copd. 18:2895-2910, 2023.

Chronic obstructive pulmonary disease (COPD) is a disease defined by
airflow obstruction with a high morbidity and mortality and significant
economic burden. Although pulmonary function testing is the cornerstone in
diagnosis of COPD, it cannot fully characterize disease severity or cause
of dyspnea because of disease heterogeneity and variable related and
comorbid conditions affecting cardiac, vascular, and musculoskeletal
systems. Cardiopulmonary exercise testing (CPET) is a valuable tool for
assessing physical function in a wide range of clinical conditions,
including COPD. Familiarity with measurements made during CPET and its
potential to aid in clinical decision-making related to COPD can thus be
useful to clinicians caring for this population. This review highlights
pulmonary and extrapulmonary impairments that can contribute to exercise
limitation in COPD. Key elements of CPET are identified with an emphasis
on measurements most relevant to COPD. Finally, clinical applications of
CPET demonstrated to be of value in the COPD setting are identified. These
include quantifying functional capacity, differentiating among potential
causes of symptoms and limitation, prognostication and risk assessment for
operative procedures, and guiding exercise prescription.

De Biase N; University of Pisa, Pisa, Italy
Mazzola M; Del Punta L; Di Fiore V; De Carlo M; Giannini C;
Costa G; Paneni F; Mengozzi A; Nesti L; Gargani L; Masi S; Pugliese NR

European Journal of Heart Failure. 25(11):1947-1958, 2023 11.

AIMS: Degenerative aortic valve stenosis with preserved ejection fraction
(ASpEF) and heart failure with preserved ejection fraction (HFpEF) display
intriguing similarities. This study aimed to provide a non-invasive,
comparative analysis of ASpEF versus HFpEF at rest and during exercise.
METHODS AND RESULTS: We prospectively enrolled 148 patients with HFpEF
and 150 patients with degenerative moderate-to-severe ASpEF, together with
66 age- and sex-matched healthy controls. All subjects received a
comprehensive evaluation at rest and 351/364 (96%) performed a combined
cardiopulmonary exercise stress echocardiography test. Patients with ASpEF
eligible for transcatheter aortic valve replacement (n = 125) also
performed cardiac computed tomography (CT). HFpEF and ASpEF patients
showed similar demographic distribution and biohumoral profiles. Most
patients with ASpEF (134/150, 89%) had severe high-gradient aortic
stenosis; 6/150 (4%) had normal-flow, low-gradient ASpEF, while 10/150
(7%) had low-flow, low-gradient ASpEF. Both patient groups displayed
significantly lower peak oxygen consumption (VO2 ), peak cardiac output,
and peak arteriovenous oxygen difference compared to controls (all p <
0.01). ASpEF patients showed several extravalvular abnormalities at rest
and during exercise, similar to HFpEF (all p < 0.01 vs. controls).
Epicardial adipose tissue (EAT) thickness was significantly greater in
ASpEF than HFpEF and was inversely correlated with peak VO2 in all groups.
In ASpEF, EAT was directly related to echocardiography-derived disease
severity and CT-derived aortic valve calcium burden.
CONCLUSION: Functional capacity is similarly impaired in ASpEF and HFpEF
due to both peripheral and central components. Further investigation is
warranted to determine whether extravalvular alterations may affect
disease progression and prognosis in ASpEF even after valve intervention,
which could support the concept of ASpEF as a specific sub-phenotype of
HFpEF.

Shah RV; Vanderbilt University Medical Center Nashville TN
Hwang SJ; Murthy VL; Zhao S; Tanriverdi K; Gajjar P; Duarte K;
Schoenike M; Farrell R; Brooks LC; Gopal DM; Ho JE; Girerd N; Vasan RS;
Levy D; Freedman JE; Lewis GD; Nayor M

Journal of the American Heart Association. 12(21):e029980, 2023 Nov 07.

BACKGROUND: While exercise impairments are central to symptoms and
diagnosis of heart failure with preserved ejection fraction (HFpEF), prior
studies of HFpEF biomarkers have mostly focused on resting phenotypes. We
combined precise exercise phenotypes with cardiovascular proteomics to
identify protein signatures of HFpEF exercise responses and new potential
therapeutic targets.
METHODS AND RESULTS: We analyzed 277 proteins (Olink) in 151 individuals
(N=103 HFpEF, 48 controls; 62+/-11 years; 56% women) with cardiopulmonary
exercise testing with invasive monitoring. Using ridge regression adjusted
for age/sex, we defined proteomic signatures of 5 physiological variables
involved in HFpEF: peak oxygen uptake, peak cardiac output, pulmonary
capillary wedge pressure/cardiac output slope, peak pulmonary vascular
resistance, and peak peripheral O2 extraction. Multiprotein signatures of
each of the exercise phenotypes captured a significant proportion of
variance in respective exercise phenotypes. Interrogating the importance
(ridge coefficient magnitude) of specific proteins in each signature
highlighted proteins with putative links to HFpEF pathophysiology (eg,
inflammatory, profibrotic proteins), and novel proteins linked to distinct
physiologies (eg, proteins involved in multiorgan [kidney, liver, muscle,
adipose] health) were implicated in impaired O2 extraction. In a separate
sample (N=522, 261 HF events), proteomic signatures of peak oxygen uptake
and pulmonary capillary wedge pressure/cardiac output slope were
associated with incident HFpEF (odds ratios, 0.67 [95% CI, 0.50-0.90] and
1.43 [95% CI, 1.11-1.85], respectively) with adjustment for clinical
factors and B-type natriuretic peptides.
CONCLUSIONS: The cardiovascular proteome is associated with precision
exercise phenotypes in HFpEF, suggesting novel mechanistic targets and
potential methods for risk stratification to prevent HFpEF early in its
pathogenesis.

Ramirez-Velez R; Hospital Universitario de Navarra, Madrid, Spain
Oscoz-Ochandorena S; Garcia-Alonso Y; Garcia-Alonso N;
Legarra-Gorgonon G; Oteiza J; Lorea AE; Izquierdo M; Correa-Rodriguez M

Clinical Nutrition ESPEN. 58:253-262, 2023 Dec.

BACKGROUND & AIMS: Long COVID syndrome (LCS) involves persistent symptoms
experienced by many patients after recovering from coronavirus disease
2019 (COVID-19). We aimed to assess skeletal muscle energy metabolism,
which is closely related to substrate oxidation rates during exercise, in
patients with LCS compared with healthy controls. We also examined whether
muscle power output mediates the relationship between COVID-19 and
skeletal muscle energy metabolism.

METHODS: In this cross-sectional study, we enrolled 71 patients with LCS
and 63 healthy controls. We assessed clinical characteristics such as body
composition, physical activity, and muscle strength. We used
cardiopulmonary exercise testing to evaluate substrate oxidation rates
during graded exercise. We performed statistical analyses to compare group
characteristics and peak fat oxidation differences based on power output.

RESULTS: The two-way analysis of covariance (ANCOVA) results, adjusted
for covariates, showed that the patients with LCS had lower absolute
maximal fatty acid oxidation (MFO), relative MFO/fat free mass (FFM),
absolute carbohydrates oxidation (CHox), relative CHox/FFM, and oxygen
uptake (VO2) at maximum fat oxidation (g min-1) than the healthy controls
(P < 0.05). Moderation analysis indicated that muscle power output
significantly influenced the relationship between LCS and reduced peak fat
oxidation (interaction beta = -0.105 [95% confidence interval -0.174;
-0.036]; P = 0.026). Therefore, when muscle power output was below 388 W,
the effect of the LCS on MFO was significant (62% in our study sample P =
0.010). These findings suggest compromised mitochondrial bioenergetics and
muscle function, represented by lower peak fat oxidation rates, in the
patients with LCS compared with the healthy controls.

CONCLUSION: The patients with LCS had lower peak fat oxidation during
exercise compared with the healthy controls, potentially indicating
impairment in skeletal muscle function. The relationship between peak fat
oxidation and LCS appears to be mediated predominantly by muscle power
output. Additional research should continue investigating LCS pathogenesis
and the functional role of mitochondria.