Wu FM; Opotowsky AR; Denhoff ER; Gongwer R; Gurvitz MZ; Landzberg MJ;
Shafer KM; Valente AM; Uluer AZ; Rhodes J.

Seminars in Thoracic & Cardiovascular Surgery. 30(4):462-469, 2018 Winter.
VI 1
Comment in: Semin Thorac Cardiovasc Surg. 2018 Winter;30(4):470-471; PMID:
30179673

While the Fontan procedure has improved life expectancy, patients with
single ventricle physiology have impaired exercise capacity due to limited
increase in pulmonary blood flow during activity. Enhancing the “thoracic
pump” using inspiratory muscle training (IMT) may ameliorate this
impairment. Adult nonsmokers with Fontan physiology were recruited through
Boston Children’s Hospital’s outpatient clinic. Participants underwent
cardiopulmonary exercise testing and pulmonary function testing, followed
by 12 weeks of IMT and then repeat testing. The primary endpoint was
change in % predicted peak oxygen consumption (VO2). Secondary endpoints
were changes in other exercise metrics. Eleven patients (6 male) were
enrolled. Median ages at time of enrollment and Fontan completion were
28.8 years (25.7, 45.5) and 7.8 years (3.9, 16.5), respectively. Average
baseline maximal inspiratory pressure (MIP) was normal; only 2 patients
had MIP <70% predicted. Peak work rate improved significantly from
baseline after 12 weeks of IMT (116.5 +/- 45.0 to 126.8 +/- 47.0 W,
P=0.019). Peak VO2 tended to improve (baseline 68.1 +/- 14.3, change + 5.3
+/- 9.6% predicted, P=0.12), as did VE/VCO2 slope (34.1 +/- 6.7 to 31.4
+/- 3.6, P=0.12). There was no change in peak tidal volume or MIP. In a
small cohort of Fontan patients with mostly normal MIP, IMT was associated
with significant improvement in peak work rate and a trend toward higher
peak VO2 and improved ventilatory efficiency. Larger studies are needed to
determine if this reflects true lack of effect or whether this pilot study
was underpowered for effect size, and whether IMT is more narrowly useful
for patients with impaired MIP.

Dougherty RJ; Lindheimer JB; Stegner AJ; Van Riper S; Okonkwo OC; Cook DB.

Journal of Alzheimer’s Disease. 61(2):601-611, 2018.
VI

Cardiorespiratory fitness (CRF) is routinely investigated in older adults;
however, the most appropriate CRF measure to use for this population has
received inadequate attention. This study aimed to 1) evaluate the
reliability and validity of the oxygen uptake efficiency slope (OUES) as a
sub-maximal measurement of CRF; 2) examine demographic, risk-factor, and
exercise testing differences in older adults who satisfied standardized
criteria for a peak oxygen consumption (VO2peak) test compared to those
who did not; and 3) determine the difference between directly measured
VO2peak values and OUES-predicted VO2peak values. One hundred ten
enrollees from the Wisconsin Registry for Alzheimer’s Prevention
participated in this study. Participants performed a graded maximal
exercise test and wore an accelerometer for 7 days. For each participant,
the OUES was calculated at 75%, 90%, and 100% of exercise duration.
VO2peak was recorded at peak effort, and one week of physical activity
behavior was measured. OUES values calculated at separate relative
exercise durations displayed excellent reliability (ICC = 0.995; p <
0.001), and were strongly correlated with VO2peak (rrange = 0.801-0.909; p
< 0.001). As hypothesized, participants who did not satisfy VO2peak
criteria were significantly older than those who satisfied criteria (p =
0.049) and attained a directly measured VO2peak that was 2.31 mL.kg.min-1
less than the value that was predicted by OUES VO2peak (p = 0.003). Older
adults are less likely to satisfy VO2peak criteria, which results in an
underestimation of their CRF. Without adhering to standardized criteria,
VO2peak measurement error may lead to misinterpretation of CRF and
age-related associations. Here, we conclude that OUES is a reliable, valid
measurement of CRF which does not require achievement of standardized
criteria.

Allen S; Brown V; Prabhu P; Scott M; Rockall T; Preston S; Sultan J;

BMJ Open [BMJ Open] 2018 Dec 22; Vol. 8 (12), pp. e023190. Date of Electronic Publication: 2018 Dec 22.

Introduction: Neoadjuvant therapy prior to oesophagogastric resection is the gold standard of care for patients with T2 and/or nodal disease. Despite this, studies have taught us that chemotherapy decreases patients’ functional capacity as assessed by cardiopulmonary exercise (CPX) testing. We aim to show that a multimodal prehabilitation programme, comprising supervised exercise, psychological coaching and nutritional support, will physically, psychologically and metabolically optimise these patients prior to oesophagogastric cancer surgery so they may better withstand the immense physical and metabolic stress placed on them by radical curative major surgery.
Methods and Analysis: This will be a prospective, randomised, controlled, parallel, single-centre superiority trial comparing a multimodal ‘prehabilitation’ intervention with ‘standard care’ in patients with oesophagogastric malignancy who are treated with neoadjuvant therapy prior to surgical resection. The primary aim is to demonstrate an improvement in baseline cardiopulmonary function as assessed by anaerobic threshold during CPX testing in an interventional (prehab) group following a 15-week preoperative exercise programme, throughout and following neoadjuvant treatment, when compared with those that undergo standard care (control group). Secondary objectives include changes in peak oxygen uptake and work rate (total watts achieved) at CPX testing, insulin resistance, quality of life, chemotherapy-related toxicity and completion, nutritional assessment, postoperative complication rate, length of stay and overall mortality.
Ethics and Dissemination: This study has been approved by the London-Bromley Research Ethics Committee and registered on ClinicalTrials.gov. The results will be disseminated in a peer-reviewed journal.

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.

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.

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.

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

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.

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.

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.