Category Archives: Publications

Oxygen consumption trajectory flattening-yet another cardiopulmonary exercise testing parameter in chronic heart failure.

Kleber FX; Köln PJ

European Journal Of Heart Failure [Eur J Heart Fail], ISSN: 1879-0844, 2018 Apr 14;

This article refers to ‘A flattening oxygen consumption
trajectory phenotypes disease severity and poor prognosis
in patients with heart failure with reduced,mid-range, and
preserved ejection fraction’ by D. Popovic et al., published
in this issue on pages xxx.
Cardiopulmonary exercise testing (CPET) has gained major importance
in heart failure (HF) units and in the evaluation of patients for
heart transplantation (HTx) or left ventricular assist device (LVAD)
implantation. While oxygen consumption at maximal effort (peak
VO2) has been accepted even far beyond the field of cardiology,
other parameters such as ventilatory efficiency,1 end-tidal partial
pressure of carbon dioxide (PETCO2)2 and exercise oscillatory
ventilation (EOV),3 have broadened the spectrum of understanding
and measurements of HF symptoms and helped in evaluation
of prognosis. Most data are derived from patients with systolic HF
and none of these parameters have conclusively helped to specifically
characterize diastolic HF, which is currently in the focus of
efforts to understand the HF epidemic.

Invasive cardiopulmonary exercise testing in the evaluation of unexplained dyspnea: Insights from a multidisciplinary dyspnea center.

Huang W, Resch S, Oliveira RK, Cockrill BA, Systrom DM,
Waxman AB

Eur J Prev Cardiol. 2017 Jul;24(11):1190-1199.

Unexplained dyspnea is a common diagnosis that often results in
repeated diagnostic testing and even delayed treatments while a determination of
the cause is being investigated. Through a retrospective study, we evaluated the
diagnostic efficacy of a multidisciplinary dyspnea evaluation center (MDEC) using
invasive cardiopulmonary exercise test to diagnose potential causes of
unexplained dyspnea.

Methods We reviewed the medical records of all patients
referred with unexplained dyspnea to the MDEC between March 2011 and October
2014. We assessed the diagnostic efficacy before and after presentation to the

Results During the study period a total of 864 patients were referred to
the MDEC and, of those, 530 patients underwent further investigation with
invasive cardiopulmonary exercise test and constituted the study sample. The
median age was 57 (44-68) years, 67.2% were women, and median body mass index was
26.22 (22.78-31.01). A diagnosis was made in 530 patients including: exercise
pulmonary arterial hypertension of 88 (16.6%), heart failure with preserved
ejection fraction of 94 (17.7%), dysautonomia 112 (21.1%), oxidative myopathy of
130 (24.5%), primary hyperventilation of 43 (8.1%), and other 58 (10.9%). The
time from initial presentation to referral was significantly longer than time to
diagnosis after referral for non-standardized conventional methods versus
diagnosis through MDEC using invasive cardiopulmonary exercise test (511 days
(292-1095 days) vs. 27 days (13-53 days), p < 0.0001). In a subgroup analysis, we
reviewed that patients referred from cardiovascular clinics were more likely to
have a greater number of diagnostic tests performed and, conversely, patients
referred from pulmonary clinics were more likely to have a greater number of
treatments prescribed before referral to MDEC.

Conclusions As a result of this
retrospective study, we have evaluated that a multidisciplinary approach that
includes invasive cardiopulmonary exercise test dramatically reduces the time to
diagnosis compared with traditional treatment and testing methods.

Running multiple marathons is not a risk factor for premature subclinical vascular impairment.

Pressler A, Suchy C, Friedrichs T, Dallinger S, Grabs V, Haller
B, Halle M, Scherr J

Eur J Prev Cardiol. 2017 Aug;24(12):1328-1335.

Background In contrast to the well-accepted benefits of moderate exercise, recent
research has suggested potential deleterious effects of repeated marathon running
on the cardiovascular system. We thus performed a comprehensive analysis of
markers of subclinical vascular damage in a cohort of runners having finished
multiple marathon races successfully.

Design This was a prospective,
observational study. Methods A total of 97 healthy male Munich marathon
participants (mean age 44 ± 10 years) underwent detailed training history,
cardiopulmonary exercise testing for assessment of peak oxygen uptake, ultrasound
for assessment of intima-media-thickness as well as non-invasive assessments of
ankle-brachial index, augmentation index, pulse wave velocity and reactive
hyperaemia index.

Results Runners had previously completed a median of eight
(range 1-500) half marathons, six (1-100) full marathons and three (1-40)
ultramarathons; mean weekly and annual training volumes were 59 ± 23 and
1639 ± 979 km. Mean peak oxygen uptake was 50 ± 8 ml/min/kg, and the Munich
marathon was finished in 3:45 ± 0:32 h. Runners showed normal mean values for
intima-media-thickness (0.60 ± 0.14 mm), ankle-brachial index (1.2 ± 0.1),
augmentation index (17 ± 13%), pulse wave velocity (8.7 ± 1.4 cm/s) and reactive
hyperaemia index (1.96 ± 0.50). Age was significantly and independently
associated with intima-media-thickness ( r = 0.531; p < 0.001), augmentation
index ( r = 0.593; p < 0.001) and pulse wave velocity ( r = 0.357; p < 0.001).
However, no independent associations of peak oxygen uptake, marathon finishing
time, number of completed races or weekly and annual training km with any of the
vascular parameters were observed.

Conclusions In this cohort of healthy male
runners, running multiple marathon races did not pose an additional risk factor
for premature subclinical vascular impairment beyond age.

Oxygen Uptake Efficiency Slope Predicts Poor Outcome in Patients With Idiopathic Pulmonary Arterial Hypertension

Tang Y, Luo Q, Liu Z, Ma X, Zhao Z, Huang Z, Gao L, Jin
Q, Xiong C, Ni X.

J Am Heart Assoc. 2017 Jun 30;6(7).

BACKGROUND: Few published studies have evaluated the power of the oxygen uptake
efficiency slope (OUES) to predict outcomes in patients with idiopathic pulmonary
arterial hypertension (IPAH), who typically die of right-sided heart failure. Our
study sought to evaluate the power of OUES to predict clinical worsening and
mortality in patients with IPAH.
METHODS AND RESULTS: Patients with newly diagnosed IPAH who underwent
symptom-limited cardiopulmonary exercise testing from November 11, 2010, to June
25, 2015, in our hospital were prospectively enrolled and followed for up to
66 months. Clinical worsening and mortality were recorded. A total of 210
patients with IPAH (159 women; mean age, 32±10 years) were studied with a median
follow-up of 41 months. Thirty-one patients died, 1 patient underwent lung
transplantation, and 85 patients presented with clinical worsening. The
univariate analysis revealed that OUES, OUESI (OUESI=OUES/body surface area),
peak oxygen uptake (V˙O2), peak V˙O2/kg, ventilation (V˙E)/carbon dioxide output
(V˙CO2) slope, peak systolic blood pressure, heart rate recovery, pulmonary
vascular resistance, cardiac index, N-terminal prohormone brain natriuretic
peptide, and World Health Organization functional class were all predictive of
clinical worsening and mortality (all P<0.05). Multivariate analysis demonstrated
that OUESI and cardiac index were independently predictive of clinical worsening,
and OUESI and N-terminal prohormone brain natriuretic peptide were independently
predictive of mortality. Patients with OUESI ≤0.52 m-2 had a worse 5-year
survival rate than patients with OUESI >0.52 m-2 (41.9% versus 89.8%, P<0.0001).
CONCLUSIONS: The OUES, a submaximal parameter obtained from cardiopulmonary
exercise testing, provides prognostic information for predicting clinical
worsening and mortality in patients with IPAH.

Cardiopulmonary fitness before and after neoadjuvant chemotherapy in patients with oesophagogastric cancer.

Navidi M;Phillips AW;Griffin SM;Duffield KE;Greystoke A;Sumpter K;Sinclair RCF;

The British Journal Of Surgery [Br J Surg] 2018 Mar 30. Date of Electronic Publication: 2018 Mar 30.

Background: Neoadjuvant chemotherapy may have a detrimental impact on cardiorespiratory reserve. Determination of oxygen uptake at the anaerobic threshold by cardiopulmonary exercise testing (CPET) provides an objective measure of cardiorespiratory reserve. Anaerobic threshold can be used to predict perioperative risk. A low anaerobic threshold is associated with increased morbidity after oesophagogastrectomy. The aim of this study was to establish whether neoadjuvant chemotherapy has an adverse effect on fitness, and whether there is recovery of fitness before surgery for oesophageal and gastric adenocarcinoma.
Methods: CPET was completed before, immediately after (week 0), and at 2 and 4 weeks after neoadjuvant chemotherapy. The ventilatory anaerobic threshold and peak oxygen uptake (Vo2 peak) were used as objective, reproducible measures of cardiorespiratory reserve. Anaerobic threshold and Vo2 peak were compared before and after neoadjuvant chemotherapy, and at the three time intervals.
Results: Some 31 patients were recruited. The mean anaerobic threshold was lower following neoadjuvant treatment: 15·3 ml per kg per min before chemotherapy versus 11·8, 12·1 and 12·6 ml per kg per min at week 0, 2 and 4 respectively (P < 0·010). Measurements were also significantly different at each time point (P < 0·010). The same pattern was noted for Vo2 peak between values before chemotherapy (21·7 ml per kg per min) and at weeks 0, 2 and 4 (17·5, 18·6 and 19·3 ml per kg per min respectively) (P < 0·010). The reduction in anaerobic threshold and Vo2 peak did not improve during the time between completion of neoadjuvant chemotherapy and surgery.
Conclusion: There was a decrease in cardiorespiratory reserve immediately after neoadjuvant chemotherapy that was sustained up to the point of surgery at 4 weeks after chemotherapy.

Exercise capacity in diabetes mellitus is predicted by activity status and cardiac size rather than cardiac function: a case control study.

Roberts TJ; Burns AT; MacIsaac RJ; MacIsaac AI; Prior DL; La Gerche A;

Cardiovascular Diabetology [Cardiovasc Diabetol] 2018 Mar 23; Vol. 17 (1), pp. 44. Date of Electronic Publication: 2018 Mar 23.

Background: The reasons for reduced exercise capacity in diabetes mellitus (DM) remains incompletely understood, although diastolic dysfunction and diabetic cardiomyopathy are often favored explanations. However, there is a paucity of literature detailing cardiac function and reserve during incremental exercise to evaluate its significance and contribution. We sought to determine associations between comprehensive measures of cardiac function during exercise and maximal oxygen consumption ([Formula: see text]peak), with the hypothesis that the reduction in exercise capacity and cardiac function would be associated with co-morbidities and sedentary behavior rather than diabetes itself.
Methods: This case-control study involved 60 subjects [20 with type 1 DM (T1DM), 20 T2DM, and 10 healthy controls age/sex-matched to each diabetes subtype] performing cardiopulmonary exercise testing and bicycle ergometer echocardiography studies. Measures of biventricular function were assessed during incremental exercise to maximal intensity.
Results: T2DM subjects were middle-aged (52 ± 11 years) with a mean T2DM diagnosis of 12 ± 7 years and modest glycemic control (HbA1c 57 ± 12 mmol/mol). T1DM participants were younger (35 ± 8 years), with a 19 ± 10 year history of T1DM and suboptimal glycemic control (HbA1c 65 ± 16 mmol/mol). Participants with T2DM were heavier than their controls (body mass index 29.3 ± 3.4 kg/m2 vs. 24.7 ± 2.9, P = 0.001), performed less exercise (10 ± 12 vs. 28 ± 30 MET hours/week, P = 0.031) and had lower exercise capacity ([Formula: see text]peak = 26 ± 6 vs. 38 ± 8 ml/min/kg, P < 0.0001). These differences were not associated with biventricular systolic or left ventricular (LV) diastolic dysfunction at rest or during exercise. There was no difference in weight, exercise participation or [Formula: see text]peak in T1DM subjects as compared to their controls. After accounting for age, sex and body surface area in a multivariate analysis, significant positive predictors of [Formula: see text]peak were cardiac size (LV end-diastolic volume, LVEDV) and estimated MET-hours, while T2DM was a negative predictor. These combined factors accounted for 80% of the variance in [Formula: see text]peak (P < 0.0001).
Conclusions: Exercise capacity is reduced in T2DM subjects relative to matched controls, whereas exercise capacity is preserved in T1DM. There was no evidence of sub-clinical cardiac dysfunction but, rather, there was an association between impaired exercise capacity, small LV volumes and sedentary behavior.

Differences in gene expression related to the results of obesity treatment, peak oxygen uptake and fatty acid metabolism measured in a cardiopulmonary exercise test.

Gruchała-Niedoszytko M; van der Vlies P; Niedoszytko P; Sanjabi B; Niedoszytko M; Kaczkan M; Pieszko M; Gierat-Haponiuk K; Śliwińska A; Szalewska D; Małgorzewicz S,

Polish Archives Of Internal Medicine [Pol Arch Intern Med] 2018 Mar 26.

INTRODUCTION The impact of obesity requires methods used on a large scale as cardiopulmonary exercise test (CPET). The gene expression may explain CPET results on molecular level.

OBJECTIVES The aim of the study was to compare gene expression in obesity, differences related to the CPET results.

PATIENTS AND METHODS The study group consisted of 9 obese and 7 controls. The treatment consisted of diet, rehabilitation, behavioural therapy. Diet was based on the body composition analysed by bioelectrical impedance (BIA), resting metabolic rate, and subjective patients’ preferences. The rehabilitation was tailored according to the CPET results: VO2peak, FAT g/h. Behavioural intervention focused on the diagnosis of health problems leading to obesity, lifestyle modification, training in self-assessment and development of healthy habits. The intensive treatment lasted for 12 weeks and consisted of consultations with a physician, dietitian and medical rehabilitation specialist. RNA was isolated from the whole blood. The analysis was performed on 47,323 transcripts, among which the high quality of the RNA was confirmed in the group of 32,379 entities. Illumina TotalPrep 96 RNA Amplification Kit was used. RESULTS The results of our study show differences in gene expression related to the CPET results indicating abnormalities in fat oxidation and maximal oxygen uptake. The genes with the crucial differences in expression were CLEC 12A, HLA DRB1, HLA DRB4, HLA-A29.1, IFIT1 LOC100133662.

CONCLUSIONS The differences in expression may be responsible for the effects of the treatment related to inflammation caused by obesity, which influences muscles, fat tissue and metabolism of fatty acids.

Surfactant proteins changes after acute hemodynamic improvement in patients with advanced chronic heart failure treated with Levosimendan.

Campodonico J; Mapelli M; Spadafora E; Ghilardi S; Agostoni P; Banfi C; Sciomer S

Respiratory Physiology & Neurobiology [Respir Physiol Neurobiol], ISSN: 1878-1519, 2018 Mar 13

Alveolar-capillary membrane evaluated by carbon monoxide diffusion (DLCO) plays an important role in heart failure (HF). Surfactant Proteins (SPs) have also been suggested as a worthwhile marker. In HF, Levosimendan improves pulmonary hemodynamics and reduces lung fluids but associated SPs and DLCO changes are unknown. Sixty-five advanced HF patients underwent spirometry, cardiopulmonary exercise test (CPET) and SPs determination before and after Levosimendan. Levosimendan caused natriuretic peptide-B (BNP) reduction, peakVO2 increase and VE/VCO2 slope reduction. Spirometry improved but DLCO did not. SP-A, SP-D and immature SP-B reduced (73.7 ± 25.3 vs. 66.3 ± 22.7 ng/mL*, 247 ± 121 vs. 223 ± 110 ng/mL*, 39.4 ± 18.7 vs. 34.4 ± 17.9AU*, respectively); while mature SP-B increased (424 ± 218 vs. 461 ± 243 ng/mL, * = p<0.001). Spirometry, BNP and CPET changes suggest hemodynamic improvement and lung fluid reduction. SP-A, SP-D and immature SP-B reduction indicates a reduction of inflammatory stress; conversely mature SP-B increase suggests alveolar cell function restoration. In conclusion, acute lung fluid reduction is associated with SPs but not DLCO changes. SPs are fast responders to alveolar-capillary membrane condition changes.

Neoadjuvant therapy reduces cardiopulmunary function in patients undegoing oesophagectomy.

Thomson IG; Wallen MP; Hall A; Ferris R; Gotley DC; Barbour AP; Lee A; Thomas J; Smithers BM

International Journal Of Surgery (London, England) [Int J Surg], ISSN: 1743-9159, 2018 Mar 16

Neoadjuvant therapy (NAT) for oesophageal cancer may reduce cardiopulmonary function, assessed by cardiopulmonary exercise testing (CPEX). Impaired cardiopulmonary function is associated with mortality following esophagectomy. We sought to assess the impact of NAT on cardiopulmonary function using CPEX and assessing the clinical relevance of any change in particular if changes were associated with post-operative morbidity. This was a prospective, cohort study of 40 patients in whom CPEX was performed before and after NAT. Thirty-eight patients underwent surgery and follow-up with perioperative outcomes measured. The primary variables derived from CPEX were the anaerobic threshold (AT) and peak oxygen uptake (V˙O2peak). There were significant reductions in the AT (pre-NAT: 12.4 ± 3.0 vs. post-NAT 10.6 ± 2.0 mL kg-1.min-1; p = 0.001). This reduction was also evident for V̇O2peak (pre-NAT: 16.6 ± 3.6 vs. post-NAT 14.9 ± 3.7 mL kg-1.min-1; p = 0.004). The relative reduction in V̇O2peak was greater in chemotherapy patients who developed any peri-operative morbidity (p = 0.04). For patients who underwent chemoradiotherapy, there was a significantly greater relative reduction in AT (p = 0.03) for those who encountered a respiratory complication. Cardiopulmonary function significantly declined as a result of NAT prior to oesophagectomy. The reduction in AT and V̇O2peak was similar in both the chemotherapy and chemoradiotherapy groups.