Category Archives: Abstracts

Routine pre- and post-neoadjuvant chemotherapy fitness testing is not indicated for oesophagogastric cancer surgery.

Drummond RJ, Vass D, Wadhawan H, Craig CF, MacKay CK, Fullarton
GM, Forshaw MJ

Ann R Coll Surg Engl. 2018 Apr 25:1-5. doi: 10.1308/rcsann.2018.0067. [Epub ahead
of print

Introduction There is a known correlation between anaerobic threshold (AT) during
cardiopulmonary exercise testing and development of cardiopulmonary complications
in high-risk patients undergoing oesophagogastric cancer surgery. This study
aimed to assess the value of routine retesting following neoadjuvant
chemotherapy.

Methods Patients undergoing neoadjuvant chemotherapy with
subsequent oesophagogastric cancer surgery with pre- and post-neoadjuvant
chemotherapy cardiopulmonary exercise data were identified from a prospectively
maintained database. Measured cardiopulmonary exercise variables included AT and
maximum oxygen uptake at peak exercise (VO2 peak). Anaerobic threshold values
within 1 ml/kg/minute were considered static. Patients were grouped into AT
ranges of less than 9 ml/kg/minute, 9-11 ml/kg/minute and greater than 11
ml/kg/minute. Outcome measures were unplanned intensive care stay, postoperative
cardiovascular morbidity and mortality.

Results Between May 2008 and August 2017,
42 patients from 675 total resections were identified, with a mean age of 65
years (range 49-84 years). Mean pre-neoadjuvant chemotherapy AT was 11.07
ml/kg/minute (standard deviation, SD, 3.24 ml/kg/minute, range 4.6-19.3
ml/kg/minute) while post-neoadjuvant chemotherapy AT was 11.19 ml/kg/minute (SD
3.05 ml/kg/minute, range 5.2-18.1 ml/kg/minute). Mean pre-neoadjuvant
chemotherapy VO2 peak was 17.13 ml/kg/minute, while post-chemotherapy this mean
fell to 16.59 ml/kg/minute. Some 44.4% of patients with a pre-chemotherapy AT
less than 9 ml/kg/minute developed cardiorespiratory complications compared with
42.2% of those whose AT was greater than 9 ml/kg/minute (P = 0.914); 63.6% of
patients in the post-neoadjuvant chemotherapy group with an AT less than 9
ml/kg/minute developed cardiorespiratory complications. There was no correlation
between direction of change in AT and outcome.

Conclusion In our patient
population, neoadjuvant chemotherapy does not appear to result in a significant
mean reduction in cardiorespiratory fitness. Routine pre- and post-neoadjuvant
chemotherapy cardiopulmonary exercise testing is currently not indicated;
however, larger studies are required to demonstrate this conclusively.

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.

Cardiopulmonary Exercise Testing in Aortic Stenosis

Le VDT

Dan Med J. 2017 May;64(5). pii: B5352.

Patients with moderate to severe aortic stenosis (AVA <1.3 cm2) who were judged,
by a referring cardiologist, as asymptomatic or equivocal symptomatic from the
aortic stenosis were included in the study. Patients with left ventricular
ejection fraction <50% were not included. Twenty-nine percent of the referred
patients were judged asymptomatic and 71% equivocal symptomatic from their valve
disease. The mean age was 72 years and 90% of the patients had an AVA-index <0.6
cm2/m2. By clinical evaluation in the outpatient clinic, 48% were judged as
having functional limitation corresponding to NYHA≥II. The study participants had
cardiopulmonary exercise testing (CPX) at inclusion, and, if relevant, pre- and
nine months post-aortic valve replacement (AVR). CPX was feasible in 130 of 131
study participants recruited across 19 months. The coefficient of variability by
test-retest was 5.4% and 4.6% for peak oxygen consumption (pVO2) and peak oxygen
pulse (pO2pulse= pVO2/peak heart rate), respectively. The stroke volume generally
increased with exercise, also in those with peak flow velocity across the aortic
valve (Vmax) >5 m/s, >4 m/s, and <4 m/s but with high valvuloarterial impedance
(Zva >5.5 mm Hg/(mL·m2 )). This was found both when assessed by inert gas
rebreathing and by the pO2pulse/hemoglobin index. Both resting and exercise
stroke volume were lower for the latter group, with Vmax <4 m/s but high
valvuloarterial impedance. A pVO2 <83% of the predicted, which corresponds to the
lower 95% percentile found in the healthy sedentary population, was predicted
independently by lower stroke volume during exercise, lower heart rate during
exercise, lower FEV1, and by higher ventilation/carbon dioxide exhaustion rate
(VE/VCO2), but not by the severity of the aortic stenosis as determined by
echocardiography. According to the CPX results, the patients were prospectively
grouped into 3 groups, as follows: 1) normal pVO2 (>83% of predicted) and
pO2pulse (>95% of predicted); 2) subnormal pVO2 or pO2pulse that according to CPX
could be explained by causes other than hemodynamic compromise; 3) subnormal pVO2
and pO2pulse. Groups 1 and 2 followed an initial conservative strategy, whereas
Group 3 was referred for angiogram and Heart Team evaluation for AVR. The
patients were followed for an average of 24 months and, in Groups 1 and 2, one
patient (0.9%) suffered cardiac death and seven were hospitalized with heart
failure (6.7%). The patient who died and another patient with heart failure had
both previously, during the study, declined AVR. For Groups 1 and 2, the rate of
the combined endpoint progression to cardiac death, hospitalization with heart
failure, or AVR was 37.5%, which seems lower than what was reported in the
literature by conventional assessment and strategy for younger asymptomatic
patients with comparable echocardiographic severity of aortic stenosis. The
endpoint progression to cardiac death, hospitalization with heart failure, or AVR
with improvement in pVO2 or in the Physical Component Score of the SF-36
health-related quality of life score was reached in 25.6% in Groups 1+2 and in
62.5% in Group 3 (p=0.003). A decreased pO2pulse, which expresses stroke volume
at peak exercise, predicted this endpoint. In 73 operated patients without left
ventricular dysfunction and no coronary stenosis, including 37 patients from the
above-mentioned study, a CPX 9 months post-AVR showed that the pVO2, on average,
was less than that predicted (mean 89% of the predicted ) and 35% of the patients
had a subnormal pVO2 (<83% of that predicted). A preoperative mean gradient <40
mm Hg across the aortic valve, the presence of atrial fibrillation, and a
permanent pacemaker post-AVR all predicted a post-AVR pVO2 <83% of that
predicted. For the 37 patients with a pre-AVR CPX, a postoperative decrease >10%
in the absolute pVO2 was noted in 30% and an increase >10% in 24% of patients. A
decrease >10% in pVO2 was predicted by preoperative mean gradient <40 mm Hg and
an increase in pVO2 was predicted by preoperative AVAI <0.4 cm2/m2 and
preoperative pO2pulse <the median in the study population (<98% of that
predicted).

CONCLUSIONS: In this group of patients, where clinical assessment is
difficult and conventional exercise testing is regarded as less useful, CPX
showed high feasibility and reproducibility. CPX therefore has potential as a
useful tool for serial monitoring. In general, the stroke volume increased during
exercise, including in patients with severe aortic stenosis or decreased resting
stroke volume. CPX gives information on hemodynamics and the physiologic
components that determine decreased pVO2. CPX seems useful to identify 1)
patients with a low risk of cardiac death and low risk of progression to symptoms
from the aortic stenosis, and 2) patients with hemodynamic compromise who improve
in functional capacity after AVR. Patients with a preoperative mean gradient <40
mm Hg across the aortic valve, with the presence of atrial fibrillation or who
have a permanent pacemaker, postoperatively seem to benefit less from AVR,
whereas the benefit seems larger in those with more severe aortic stenosis and a
decreased pO2pulse. These findings may be of importance for decisions and
information of patients before AVR.

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.

Background
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
MDEC.

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.