Author Archives: Paul Older

Cardiorespiratory Fitness and Cardiovascular Disease – the Past, Present, and Future.

Kaminsky LA; Arena R; Ellingsen Ø; Harber MP; Myers J; Ozemek C; Ross R;

Progress In Cardiovascular Diseases [Prog Cardiovasc Dis] 2019 Jan 09. Date of Electronic Publication: 2019 Jan 09.

The importance of cardiorespiratory fitness (CRF) is now well established and it is increasingly being recognized as an essential variable which should be assessed in health screenings. The key findings that have established the clinical significance of CRF are reviewed in this report, along with an overview of the current relevance of exercise as a form of medicine that can provide a number of positive health outcomes, including increasing CRF. Current assessment options for assessing CRF are also reviewed, including the direct measurement via cardiopulmonary exercise testing which now can be interpreted with age and sex-specific reference values. Future directions for the use of CRF and related measures are presented.

Efficacy of Cardiac Rehabilitation in Heart Failure Patients With Low Body Mass Index.

Marume K; Takashio S; Nakanishi M; Kumasaka L; Fukui S; Nakao K; Arakawa T; Yanase M; Noguchi T; Yasuda S; Goto Y;

Circulation Journal: Official Journal Of The Japanese Circulation Society [Circ J] 2019 Jan 16. Date of Electronic Publication: 2019 Jan 16.

Background: Low body mass index (BMI) is a relevant prognostic factor for heart failure (HF), but HF patients with low BMI are reported to be at risk of not receiving optimal drug treatment. We sought to evaluate the efficacy of cardiac rehabilitation (CR) in patients with low vs. normal BMI. Methods and Results: We studied 152 consecutive patients (low BMI, n=32; normal BMI, n=119) who participated in a 3-month CR program. Low BMI was defined as <18.5 kg/m2and normal BMI, as 18.5≤BMI<25 kg/m2. All patients underwent cardiopulmonary exercise testing and muscle strength testing at the beginning and end of the 3-month CR program. After CR, a significantly greater proportion of HF patients with low BMI had a positive change in peak V̇O2than in the normal BMI group (91% vs. 70%; P=0.010). Average percent change in peak V̇O2was significantly greater in patients with low vs. normal BMI (17.1±2.8% vs. 7.8±1.5%; P<0.001). In addition, on multivariable logistic regression, low BMI was an independent predictor of a positive change in peak V̇O2after CR (OR, 3.97; 95% CI: 1.10-14.31; P=0.035).
Conclusions: CR has a greater effect in patients with low than normal BMI, and low BMI is an independent predictor of a positive change in peak V̇O2. Thus, CR should be strongly recommended for HF patients with low BMI.

A survey of UK peri-operative medicine: pre-operative care.

Bougeard AM, Brent A, Swart M, Snowden C

Anaesthesia. 2017 Aug;72(8):1010-1015. doi: 10.1111/anae.13934. Epub 2017 Jun 14.

The majority of UK hospitals now have a Local Lead for Peri-operative Medicine (n
= 115). They were asked to take part in an online survey to identify provision
and practice of pre-operative assessment and optimisation in the UK. We received
86 completed questionnaires (response rate 75%). Our results demonstrate
strengths in provision of shared decision-making clinics. Fifty-seven (65%, 95%CI
55.8-75.4%) had clinics for high-risk surgical patients. However, 80 (93%,
70.2-87.2%) expressed a desire for support and training in shared
decision-making. We asked about management of pre-operative anaemia, and
identified that 69 (80%, 71.5-88.1%) had a screening process for anaemia, with
72% and 68% having access to oral and intravenous iron therapy, respectively. A
need for peri-operative support in managing frailty and cognitive impairment was
identified, as few (24%, 6.5-34.5%) respondents indicated that they had access to
specific interventions. Respondents were asked to rank their ‘top five’ priority
topics in Peri-operative Medicine from a list of 22. These were: shared
decision-making; peri-operative team development; frailty screening and its
management; postoperative morbidity prediction; and primary care collaboration.
We found variation in practice across the UK, and propose to further explore this
variation by examining barriers and facilitators to improvement, and highlighting
examples of good practice.

Increased physiological dead space at exercise is a marker of mild pulmonary or cardiovascular disease in dyspneic subjects.

Plantier L; Delclaux C;

European Clinical Respiratory Journal [Eur Clin Respir J] 2018 Jul 05; Vol. 5 (1), pp. 1492842. Date of Electronic Publication: 20180705 (Print Publication: 2018).

Background: The characteristics of cardiopulmonary exercise testing (CPET)-derived parameters for the differential diagnosis of exertional dyspnea are not well known.
Objectives: We hypothesized that increased physiological dead space ventilation (VD/Vt) is a marker for mild pulmonary or cardiovascular disease in patients with exertional dyspnea.
Design: We used receiver operating characteristic analysis to determine the performance of individual CPET parameters for identifying subjects with either mild pulmonary or cardiovascular disease, among 77 subjects with mild-to-moderate exertional dyspnea (modified Medical Research Council scale 1-2).
Results: In comparison with subjects without disease, subjects with pulmonary disease (n = 31) had higher VE/V’CO2 slope, higher VD/Vt, and lower ventilatory reserve. Subjects with cardiovascular disease (n = 14) had lower heart rate and cardiovascular double product and higher VD/Vt at peak exercise. At a threshold of 28%, the sensitivity and specificity of VD/Vt at peak exercise for identifying pulmonary or cardiovascular disease were 89% (95% CI: 64-98%) and 72% (95% CI: 46-89%), respectively.
Conclusions: Increased physiological VD/Vt at exercise is a sensitive and specific marker of mild pulmonary or cardiovascular disease in dyspneic subjects

Predictive Capability of Cardiopulmonary and Exercise Parameters From Day 1 to 6 Months After Acute Pulmonary Embolism.

Habedank D; Opitz C; Karhausen T; Kung T; Steinke I; Ewert R;

Clinical Medicine Insights. Circulatory, Respiratory And Pulmonary Medicine [Clin Med Insights Circ Respir Pulm Med] 2018 Aug 16; Vol. 12, pp. 1179548418794155. Date of Electronic Publication: 20180816 (Print Publication: 2018).

We hypothesized that the slope of relation ventilation to carbon dioxide output (V’E/V’CO2-slope) could be predictive already during the very first days after submassive pulmonary embolism (PE) to right ventricular systolic pressure (RVsys by echocardiography) after 6 months. We evaluated 21 hemodynamically stable patients at admittance, at days 3, 7, 90, and 180 by cardiopulmonary exercise testing and echocardiography. V’E/V’CO2-slope (48.4 ± 10.8) decreased within the first week (43.0 ± 9.8 at day 7) and normalized until follow-up at 6 months (35.0 ± 11.3; P < 10-4), p(a-ET)CO2 remained abnormal between days 1 and 3 (5.0 ± 3.9 to 6.7 ± 5.3 mmHg). RVsys declined from 41.7 ± 14.3 to 26.3±13.1 mmHg (P < 10-4) at 6 months. V’E/V’CO2-slope (r²= 0.27; P < .02) and RVsys (r² = 0.28; P = .03) at day 7 correlated with RVsys at 6 months. p(a-ET)CO2, p(a-ET)O2, V’D/V’T were not related to RVsys after 6 months. RVsys 6 months after acute PE is positively correlated with the V’E/V’CO2-slope at day 7.

C-Reactive Protein and N-Terminal Pro-brain Natriuretic Peptide Levels Correlate With Impaired Cardiorespiratory Fitness in Patients With Heart Failure Across a Wide Range of Ejection Fraction.

van Wezenbeek J; Canada JM; Ravindra K; Carbone S; Trankle CR; Kadariya D; Buckley LF; Del Buono M; Billingsley H; Viscusi M; Wohlford GF; Arena R; Van Tassell B; Abbate A;

Frontiers In Cardiovascular Medicine [Front Cardiovasc Med] 2018 Dec 21; Vol. 5, pp. 178. Date of Electronic Publication: 20181221 (Print Publication: 2018).

Background: Impaired cardiorespiratory fitness (CRF) is a hallmark of heart failure (HF). Serum levels of C-reactive protein (CRP), a systemic inflammatory marker, and of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of myocardial strain, independently predict adverse outcomes in HF patients. Whether CRP and/or NT-proBNP also predict the degree of CRF impairment in HF patients across a wide range of ejection fraction is not yet established.
Methods: Using retrospective analysis, 200 patients with symptomatic HF who completed one or more treadmill cardiopulmonary exercise tests (CPX) using a symptom-limited ramp protocol and had paired measurements of serum high-sensitivity CRP and NT-proBNP on the same day were evaluated. Univariate and multivariate correlations were evaluated with linear regression after logarithmic transformation of CRP (log10) and NT-proBNP (logN).
Results: Mean age of patients was 57 ± 10 years and 55% were male. Median CRP levels were 3.7 [1.5-9.0] mg/L, and NT-proBNP levels were 377 [106-1,464] pg/ml, respectively. Mean peak oxygen consumption (peak VO2) was 16 ± 4 mlO2•kg-1•min-1. CRP levels significantly correlated with peakVO2 in all patients (R = -0.350, p < 0.001) and also separately in the subgroup of patients with reduced left ventricular ejection fraction (LVEF) (HFrEF, N = 109) (R = -0.282, p < 0.001) and in those with preserved EF (HFpEF, N = 57) (R = -0.459, p < 0.001). NT-proBNP levels also significantly correlated with peak VO2 in all patients (R = -0.330, p < 0.001) and separately in patients with HFrEF (R = -0.342, p < 0.001) and HFpEF (R = -0.275, p = 0.032). CRP and NT-proBNP did not correlate with each other (R = 0.05, p = 0.426), but independently predicted peak VO2 (R = 0.421, p < 0.001 and p < 0.001, respectively).
Conclusions: Biomarkers of inflammation and myocardial strain independently predict peak VO2 in HF patients. Anti-inflammatory therapies and therapies alleviating myocardial strain may independently improve CRF in HF patients across a large spectrum of LVEF.

Reproducibility of Inert Gas Rebreathing Method to Estimate Cardiac Output at Rest and During Cardiopulmonary Exercise Stress Testing.

Okwose NC; Zhang J; Chowdhury S; Houghton D; Ninkovic S; Jakovljević S; Jevtic B; Ropret R; Eggett C; Bates M;MacGowan G; Jakovljevic D;

International Journal Of Sports Medicine [Int J Sports Med] 2019 Jan 03. Date of Electronic Publication: 2019 Jan 03.

The present study evaluated reproducibility of the inert gas rebreathing method to estimate cardiac output at rest and during cardiopulmonary exercise testing. Thirteen healthy subjects (10 males, 3 females, ages 23-32 years) performed maximal graded cardiopulmonary exercise stress test using a cycle ergometer on 2 occasions (Test 1 and Test 2). Participants cycled at 30-watts/3-min increments until peak exercise. Hemodynamic variables were assessed at rest and during different exercise intensities (i. e., 60, 120, 150, 180 watts) using an inert gas rebreathing technique. Cardiac output and stroke volume were not significantly different between the 2 tests at rest 7.4 (1.6) vs. 7.1 (1.2) liters min-1, p=0.54; 114 (28) vs. 108 (15) ml beat-1, p=0.63) and all stages of exercise. There was a significant positive relationship between Test 1 and Test 2 cardiac outputs when data obtained at rest and during exercise were combined (r=0.95, p<0.01 with coefficient of variation of 6.0%), at rest (r=0.90, p<0.01 with coefficient of variation of 5.1%), and during exercise (r=0.89, p<0.01 with coefficient of variation 3.3%). The mean difference and upper and lower limits of agreement between repeated measures of cardiac output at rest and peak exercise were 0.4 (-1.1 to 1.8) liter min-1 and 0.5 (-2.3 to 3.3) liter min-1, respectively. The inert gas rebreathing method demonstrates an acceptable level of test-retest reproducibility for estimating cardiac output at rest and during cardiopulmonary exercise testing at higher metabolic demands.

Cardiorespiratory fitness data from 18,189 participants who underwent treadmill cardiopulmonary exercise testing in a Brazilian population.

Rossi Neto JM; Tebexreni AS; Alves ANF; Smanio PEP; de Abreu FB; Thomazi MC; Nishio PA; Cuninghant IA;

Plos One [PLoS One] 2019 Jan 09; Vol. 14 (1), pp. e0209897. Date of Electronic Publication: 20190109 (Print Publication: 2019).

Purpose: Cardiorespiratory fitness is inversely associated with a high risk of cardiovascular disease, all-cause mortality, and mortality attributable to various cancers. It is often estimated indirectly using mathematical formulas for estimating oxygen uptake. Cardiopulmonary exercise testing, especially oxygen uptake, represents the “gold standard” for assessing exercise capacity. The purpose of this report was to develop reference standards for exercise capacity by establishing cardiorespiratory fitness values derived from cardiopulmonary exercise testing in a Brazilian population. We focused on oxygen uptake standards and compared the maximal oxygen uptake [mLO2·kg-1·min-1] values with those in the existing literature.
Methods: A database was constructed using reports from cardiopulmonary exercise testing performed at Fleury laboratory. The final cohort included 18,189 individuals considered to be free of structural heart disease. Percentiles of maximal oxygen uptake for men and women were determined for six age groups between 7 and 84 years. We compared the values with existing reference data from patients from Norway and the United States.
Results: There were significant differences in maximal oxygen uptake between sexes and across the age groups. In our cohort, the 50th percentile maximal oxygen uptake values for men and women decreased from 44.7 and 36.3 mLO2·kg-1·min-1 to 28.4 and 22.3 mLO2·kg-1·min-1 for patients aged 20-29 years to patients aged 60-69 years, respectively. For each age group, both Norwegian men and women had greater cardiorespiratory fitness than cohorts in the United States and Brazil.
Conclusion: To our knowledge, our analysis represents the largest reference data for cardiorespiratory fitness based on treadmill cardiopulmonary exercise testing. Our findings provide reference values of maximal oxygen uptake measurements from treadmill tests in Brazilian populations that are more accurate than previous standard values based on workload-derived estimations. This data may also add information to the global data used for the interpretation of cardiorespiratory fitness.

Inter-observer reliability of preoperative cardiopulmonary exercise test interpretation: a cross-sectional study.

Abbott TEF, Gooneratne M, McNeill J, Lee A, Levett DZH, Grocott
MPW, Swart M, MacDonald N; ARCTIC study investigators.

Br J Anaesth. 2018 Mar;120(3):475-483. doi: 10.1016/j.bja.2017.11.071. Epub 2017
Nov 29.

BACKGROUND: Despite the increasing importance of cardiopulmonary exercise testing
(CPET) for preoperative risk assessment, the reliability of CPET interpretation
is unclear. We aimed to assess inter-observer reliability of preoperative CPET.
METHODS: We conducted a prospective, multi-centre, observational study of
preoperative CPET interpretation. Participants were professionals with previous
experience or training in CPET, assessed by a standardized questionnaire. Each
participant interpreted 100 tests using standardized software. The CPET variables
of interest were oxygen consumption at the anaerobic threshold (AT) and peak
oxygen consumption (VO2 peak). Inter-observer reliability was measured using
intra-class correlation coefficient (ICC) with a random effects model. Results
are presented as ICC with 95% confidence interval, where ICC of 1 represents
perfect agreement and ICC of 0 represents no agreement.
RESULTS: Participants included 8/28 (28.6%) clinical physiologists, 10 (35.7%)
junior doctors, and 10 (35.7%) consultant doctors. The median previous experience
was 140 (inter-quartile range 55-700) CPETs. After excluding the first 10 tests
(acclimatization) for each participant and missing data, the primary analysis of
AT and VO2 peak included 2125 and 2414 tests, respectively. Inter-observer
agreement for numerical values of AT [ICC 0.83 (0.75-0.90)] and VO2 peak [ICC
0.88 (0.84-0.92)] was good. In a post hoc analysis, inter-observer agreement for
identification of the presence of a reportable AT was excellent [ICC 0.93
(0.91-0.95)] and a reportable VO2 peak was moderate [0.73 (0.64-0.80)].
CONCLUSIONS: Inter-observer reliability of interpretation of numerical values of
two commonly used CPET variables was good (>80%). However, inter-observer
agreement regarding the presence of a reportable value was less consistent.

Perioperative cardiopulmonary exercise testing (CPET): consensus clinical guidelines on indications, organization, conduct, and physiological interpretation.

Levett DZH, Jack S, Swart M, Carlisle J, Wilson J, Snowden C,
Riley M, Danjoux G, Ward SA, Older P, Grocott MPW; Perioperative
Exercise Testing and Training Society (POETTS).

Br J Anaesth. 2018 Mar;120(3):484-500. doi: 10.1016/j.bja.2017.10.020. Epub 2017
Nov 24.

The use of perioperative cardiopulmonary exercise testing (CPET) to evaluate the
risk of adverse perioperative events and inform the perioperative management of
patients undergoing surgery has increased over the last decade. CPET provides an
objective assessment of exercise capacity preoperatively and identifies the
causes of exercise limitation. This information may be used to assist clinicians
and patients in decisions about the most appropriate surgical and non-surgical
management during the perioperative period. Information gained from CPET can be
used to estimate the likelihood of perioperative morbidity and mortality, to
inform the processes of multidisciplinary collaborative decision making and
consent, to triage patients for perioperative care (ward vs critical care), to
direct preoperative interventions and optimization, to identify new
comorbidities, to evaluate the effects of neoadjuvant cancer therapies, to guide
prehabilitation and rehabilitation, and to guide intraoperative anaesthetic
practice. With the rapid uptake of CPET, standardization is key to ensure valid,
reproducible results that can inform clinical decision making. Recently, an
international Perioperative Exercise Testing and Training Society has been
established (POETTS www.poetts.co.uk) promoting the highest standards of care for
patients undergoing exercise testing, training, or both in the perioperative
setting. These clinical cardiopulmonary exercise testing guidelines have been
developed by consensus by the Perioperative Exercise Testing and Training Society
after systematic literature review. The guidelines have been endorsed by the
Association of Respiratory Technology and Physiology (ARTP).