Category Archives: Publications

Type 2 Diabetes Mellitus, Glycated Hemoglobin Levels, and Cardiopulmonary Exercise Capacity in Patients With Ischemic Heart Disease.

Uribe-Heredia G; Arroyo-Espliguero R; Viana-Llamas MC; Piccone-Saponara LG; Álvaro-Fernández H;
García-Magallón B; Torán-Martínez C; Silva-Obregón A; Izquierdo-Alonso JL

Journal Of Cardiopulmonary Rehabilitation And Prevention [J Cardiopulm Rehabil Prev] 2019 Nov 08. Date of Electronic Publication: 2019 Nov 08.

Purpose: Diabetes mellitus (DM) is associated with long-term cardiovascular complications, including ischemic heart disease (IHD). Nonetheless, DM may directly impair myocardial and lung structure and function. The aim of this study was to assess the impact of type 2 DM (T2DM) and glycemic control on cardiopulmonary exercise capacity in patients with IHD.
Methods: The study involved a cross-sectional analysis of 91 consecutive patients (57 ± 10 yr, 90% men) who underwent a cardiopulmonary exercise test at the beginning of an exercise-based standard phase-II cardiac rehabilitation program, 2 to 3 mo after an acute coronary syndrome. Association of T2DM with cardiopulmonary exercise test parameters was assessed using multiple linear regression analysis controlling for prespecified potential confounders.
Results: There were 26 (29%) diabetic subjects among IHD patients included in the study. After adjustment, T2DM was an independent predictor of a reduced peak oxygen uptake (VO2peak) (P = .005), a reduced pulse O2 trajectory (P = .001), a steeper minute ventilation to carbon dioxide output (VE/VCO2) slope (P = .046), and an increased dead space-to-tidal volume ratio (VD/VT) at peak exercise (P = .049). Glycated hemoglobin (HbA1c) levels were significantly associated with a reduced forced expiratory volume in the first second of expiration (FEV1) (P = .013), VE (P = .001), and VT (P = .007). VO2peak (P trend < .001), VO2 at anaerobic threshold (P trend < .001), and pulse O2 trajectory (P trend < .001) decreased among HbA1c tertiles.
Conclusions: Patients with IHD and a previous diagnosis of T2DM had a reduced aerobic capacity and a ventilation-perfusion mismatch compared with nondiabetic patients. Poor glycemic control in men further deteriorates aerobic capacity probably due to ventilatory inefficiency

Veterans with Gulf War Illness exhibit distinct respiratory patterns during maximal cardiopulmonary exercise.

Lindheimer JB; Cook DB; Klein-Adams JC; Qian W; Hill HZ; Lange G; Ndirangu DS; Wylie GR; Falvo MJ;

Plos One [PLoS One] 2019 Nov 12; Vol. 14 (11), pp. e0224833. Date of Electronic Publication: 20191112 (Print Publication: 2019).

Introduction: The components of minute ventilation, respiratory frequency and tidal volume, appear differentially regulated and thereby afford unique insight into the ventilatory response to exercise. However, respiratory frequency and tidal volume are infrequently reported, and have not previously been considered among military veterans with Gulf War Illness. Our purpose was to evaluate respiratory frequency and tidal volume in response to a maximal cardiopulmonary exercise test in individuals with and without Gulf War Illness.
Materials and Methods: 20 cases with Gulf War Illness and 14 controls participated in this study and performed maximal cardiopulmonary exercise test on a cycle ergometer. Ventilatory variables (minute ventilation, respiratory frequency and tidal volume) were obtained and normalized to peak exercise capacity. Using mixed-design analysis of variance models, with group and time as factors, we analyzed exercise ventilatory patterns for the entire sample and for 11 subjects from each group matched for race, age, sex, and height.
Results: Despite similar minute ventilation (p = 0.57, η2p = 0.01), tidal volume was greater (p = 0.02, η2p = 0.16) and respiratory frequency was lower (p = 0.004, η2p = 0.24) in Veterans with Gulf War Illness than controls. The findings for respiratory frequency remained significant in the matched subgroup (p = 0.004, η2p = 0.35).
Conclusion: In our sample, veterans with Gulf War Illness adopt a unique exercise ventilatory pattern characterized by reduced respiratory frequency, despite similar ventilation relative to controls. Although the mechanism(s) by which this pattern is achieved remains unresolved, our findings suggest that the components of ventilation should be considered when evaluating clinical conditions with unexplained exertional symptoms.

Limited Exercise Capacity in Patients with Systemic Sclerosis: Identifying Contributing Factors with Cardiopulmonary Exercise Testing.

Martis N, Queyrel-Moranne V, Launay D, Neviere R, Fuzibet JG, Marquette CH, Leroy S

J Rheumatol. 2018 Jan;45(1):95-102. doi: 10.3899/jrheum.161349. Epub 2017 Nov 1.

OBJECTIVE: Exercise limitation in patients with systemic sclerosis (SSc) is often
multifactorial and related to complications such as interstitial lung disease
(ILD), pulmonary vasculopathy (PV), left ventricular dysfunction (LVD), and/or
peripheral/muscular limitation (PML). We hypothesized that cardiopulmonary
exercise testing (CPET) could not only suggest and rank competing etiologies, but
also highlight peripheral impairment.
METHODS: Clinical, resting pulmonary function testing, and CPET data from
patients with SSc referred for exercise limitation between October 2009 and
November 2015 were retrospectively analyzed in this bi-center study. Patients
were categorized as having ILD, PV, LVD, and/or PML based on CPET response
patterns and the diagnoses were matched with results from the reference
investigations. The latter consisted of transthoracic echocardiography, chest
computed tomography scan, and right heart catheterization (RHC).
RESULTS: Twenty-seven patients presented with CPET profiles consistent with ILD
(n = 16), PV (n = 15), LVD (n = 5), and PML (n = 19). None of the subjects had a
normal CPET profile. There was a statistically significant negative correlation
between resting DLCO, on the one hand, and dead space to tidal volume ratio and
alveolar-arterial gradient [P(Ai-a)O2] on the other (p < 0.005). CPET identified
90% of patients with a mean pulmonary arterial pressure at rest ≥ 21 mmHg
measured by RHC (n = 10). Peak P(Ai-a)O2, taken independently from other
variables, was crucial in distinguishing subjects with ILD from those without ILD
(p < 0.05).
CONCLUSION: CPET is useful for the characterization of multifactorial exercise
limitation in patients with SSc and in identifying SSc-related complications such
as ILD and PV. This study also identifies PML as an underestimated cause of
exercise limitation.

Exercise testing for assessment of heart failure in adults with congenital heart disease.

Burstein DS; Menachem JN; Opotowsky AR;

Heart Failure Reviews [Heart Fail Rev] 2019 Nov 04. Date of Electronic Publication: 2019 Nov 04.

Congenital heart disease (CHD)-related heart failure is common and associated with significant morbidity, mortality, and resource utilization. In adults with CHD (ACHD), exercise limitation is often underestimated. Quantitative assessment with cardiopulmonary exercise testing (CPET) provides a comprehensive evaluation of exercise capacity and can help risk stratify patients, particularly across serial testing. CPET parameters must be interpreted within the context of the underlying anatomy, specifically for patients with either single ventricle physiology and/or cyanosis. Acknowledging differences in CPET parameters between ACHD and non-ACHD patients with heart failure are also important considerations when evaluating the overall benefit of advanced heart failure therapies. CPET testing can also guide safe exercise recommendation, including those with ACHD-related heart failure.

Post-discharge impact and cost-consequence analysis of prehabilitation in high-risk patients undergoing major abdominal surgery: secondary results from a randomised controlled trial

Barberan-Garcia, A.Ubre, M.Pascual-Argente, N.Risco, R.Faner, J.Balust, J.Lacy, A. M.Puig-Junoy, J.Roca,
Martinez-Palli, G.

Br J Anaesth. 2019;123(4):450-456.

BACKGROUND: Prehabilitation may reduce postoperative complications, but sustainability of its health benefits and impact on costs needs further evaluation. Our aim was to assess the midterm clinical impact and costs from a hospital perspective of an endurance-exercise-training-based prehabilitation programme in high-risk patients undergoing major digestive surgery.
METHODS: A cost-consequence analysis was performed using secondary data from a randomised, blinded clinical trial. The main outcomes assessed were (i) 30-day hospital readmissions, (ii) endurance time (ET) during an exercise testing, and (iii) physical activity by the Yale Physical Activity Survey (YPAS). Healthcare use for the cost analysis included costs of the prehabilitation programme, hospitalisation, and 30-day emergency room visits and hospital readmissions.
RESULTS: We included 125 patients in an intention-to-treat analysis. Prehabilitation showed a protective effect for 30-day hospital readmissions (relative risk: 6.4; 95% confidence interval [CI]: 1.4-30.0). Prehabilitation-induced enhancement of ET and YPAS remained statistically significant between groups at the end of the 3 and 6 month follow-up periods, respectively (DeltaET 205 [151] s; P=0.048) (DeltaYPAS 7 [2]; P=0.016). The mean cost of the programme was euro389 per patient and did not increment the total costs of the surgical process (euro812; CI: 95% -878 – 2642; P=0.365).
CONCLUSIONS: Prehabilitation may result in health value generation. Moreover, it appears to be a protective intervention for 30-day hospital readmissions, and its effects on aerobic capacity and physical activity may show sustainability at midterm.

Sex Differences in Cardiometabolic Traits and Determinants of Exercise Capacity in Heart Failure With Preserved Ejection Fraction.

Lau ES, Cunningham T, Hardin KM, Liu E, Malhotra R, Nayor M, Lewis GD, Ho JE

JAMA Cardiol. 2019 Oct 30. doi: 10.1001/jamacardio.2019.4150. [Epub ahead of

Importance: Sex differences in heart failure with preserved ejection fraction
(HFpEF) have been established, but insights into the mechanistic drivers of these
differences are limited.
Objective: To examine sex differences in cardiometabolic profiles and exercise
hemodynamic profiles among individuals with HFpEF.
Design, Setting, and Participants: This cross-sectional study was conducted at a
single-center tertiary care referral hospital from December 2006 to June 2017 and
included 295 participants who met hemodynamic criteria for HFpEF based on
invasive cardiopulmonary exercise testing results. We examined sex differences in
distinct components of oxygen transport and utilization during exercise using
linear and logistic regression models. The data were analyzed from June 2018 to
May 2019.
Main Outcomes and Measures: Resting and exercise gas exchange and hemodynamic
parameters obtained during cardiopulmonary exercise testing.
Results: Of 295 participants, 121 (41.0%) were men (mean [SD] age, 64 [12] years)
and 174 (59.0%) were women (mean [SD] age, 61 [13] years). Compared with men,
women with HFpEF in this tertiary referral cohort had fewer comorbidities,
including diabetes, insulin resistance, and hypertension, and a more favorable
adipokine profile. Exercise capacity was similar in men and women (percent
predicted peak oxygen [O2] consumption: 66% in women vs 68% in men; P = .38), but
women had distinct deficits in components of the O2 pathway, including worse
biventricular systolic reserve (multivariable-adjusted analyses: ΔLVEF β = -1.70;
SE, 0.86; P < .05; ΔRVEF β = -2.39, SE=0.80; P = .003), diastolic reserve
(PCWP/CO: β = 0.63; SE, 0.31; P = .04), and peripheral O2 extraction (C(a-v)O2
β=-0.90, SE=0.22; P < .001)).
Conclusions and Relevance: Despite a lower burden of cardiometabolic disease and
a similar percent predicted exercise capacity, women with HFpEF demonstrated
greater cardiac and extracardiac deficits, including systolic reserve, diastolic
reserve, and peripheral O2 extraction. These sex differences in cardiac and
skeletal muscle responses to exercise may illuminate the pathophysiology
underlying the development of HFpEF and should be investigated further.

Poor ventilatory efficiency during exercise may predict prolonged air leak after pulmonary lobectomy.

Brat K;Chobola M; Homolka P; Heroutova M; Benej M; Mitas L; Olson LJ; Cundrle I;

Interactive Cardiovascular And Thoracic Surgery [Interact Cardiovasc Thorac Surg] 2019 Oct 19. Date of Electronic Publication: 2019 Oct 19.

Poor ventilatory efficiency, defined as the increase in minute ventilation relative to carbon dioxide production during exercise (VE/VCO2 slope), may be associated with dynamic hyperinflation and thereby promote the development of prolonged air leak (PAL) after lung resection. Consecutive lung lobectomy candidates (n = 96) were recruited for this prospective two-centre study. All subjects underwent pulmonary function tests and cardiopulmonary exercise testing prior to surgery. PAL was defined as the presence of air leaks from the chest tube on the 5th postoperative day and developed in 28 (29%) subjects. Subjects with PAL were not different in terms of age, sex, American Society of Anesthesiologists class, type of surgery (thoracotomy/video-assisted thoracoscopic surgery) and site of surgery (right/left lung; upper/lower lobes). Subjects with PAL had more frequent pleural adhesions (50% vs 21%; P = 0.006) and steeper VE/VCO2 slope (35 ± 7 vs 30 ± 5; P = 0.001). Stepwise logistic regression showed that only the presence of pleural adhesions [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.4-10.9; P = 0.008] and VE/VCO2 slope (OR 1.1, 95% CI 1.0-1.2; P = 0.003) were independently associated with PAL (AUC 0.74, 95% CI 0.62-0.86). We conclude that a high VE/VCO2 slope during exercise may be helpful in identifying patients at greater risk for the development of PAL after lung lobectomy. Clinical trial registration number: identifier: NCT03498352.

Cardiopulmonary exercise testing in a combined screening approach to individuate pulmonary arterial hypertension in systemic sclerosis.

Santaniello A; Casella R; Vicenzi M; Rota I; Montanelli G; Santis M; Bellocchi C;  Lombardi F; Beretta L;

Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2019 Oct 21. Date of Electronic Publication: 2019 Oct 21.

Objectives: The DETECT algorithm has been developed to identify SSc patients at risk for pulmonary arterial hypertension (PAH) yielding high sensitivity but low specificity, and positive predictive value. We tested whether cardiopulmonary exercise testing (CPET) could improve the performance of the DETECT screening strategy.
Methods: Consecutive SSc patients over a 30-month period were screened with the DETECT algorithm and positive subjects were referred for CPET before the execution of right-heart catheterization. The predictive performance of CPET on top of DETECT was evaluated and internally validated via bootstrap replicates.
Results: Out of 314 patients, 96 satisfied the DETECT application criteria and 54 were positive. PAH was ascertained in 17 (31.5%) and pre-capillary pulmonary hypertension in 23 (42.6%) patients. Within CPET variables, the slope of the minute ventilation to carbon dioxide production relationship (VE/VCO2 slope) had the best performance to predict PAH at right-heart catheterization [median (interquartile range) of specificity 0.778 (0.714-0.846), positive predictive value 0.636 (0.556-0.750)]; exploratory analysis on pre-capillary yielded a specificity of 0.714 (0.636-0.8) and positive predictive value of 0.714 (0.636-0.8).
Conclusion: In association with the DETECT algorithm, CPET may be considered as a useful tool in the workup of SSc-related pulmonary hypertension. The sequential determination of the VE/VCO2 slope in DETECT-positive subjects may reduce the number of unnecessary invasive procedures without any loss in the capability to capture PAH. This strategy had also a remarkable performance in highlighting the presence of pre-capillary pulmonary hypertension.

Effects of sitagliptin on exercise capacity and hemodynamics in patients with type 2 diabetes mellitus and coronary artery disease.

Fujimoto N; Moriwaki K; Takeuchi T;  Sawai T; Sato Y; Kumagai N; Masuda J; Nakamori S; Ito M; Dohi K;

Heart And Vessels [Heart Vessels] 2019 Oct 22. Date of Electronic Publication: 2019 Oct 22.

Sitagliptin attenuates left ventricular (LV) dysfunction and may improve oxygen uptake in animals. The effects of sitagliptin on oxygen uptake (VO2) and exercise hemodynamics have been unclear in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). Thirty patients with T2DM and CAD were randomized into a sitagliptin (50 mg/day) or voglibose (0.6 mg/day) group. Patients underwent maximal cardiopulmonary exercise testing. VO2 and hemodynamics were evaluated at rest, anaerobic threshold and peak exercise. Resting LV diastolic function (E’, peak early diastolic mitral annular velocity) and geometry were evaluated by echocardiography, and endothelial function by reactive hyperemia peripheral arterial tonometry. A total of 24 patients (69 ± 9 years) completed 6 months of intervention. Peak VO2 in the sitagliptin and voglibose groups (25.3 ± 7.3 vs. 24.0 ± 7.4, 22.7 ± 4.8 vs. 22.1 ± 5.2 ml/kg/min) was slightly decreased after 6 months (time effect p = 0.051; group × time effect p = 0.49). No effects were observed on LV ejection fraction, E’, or reactive hyperemia index in either group. Heart rate during exercise was unaffected in both groups. Systolic blood pressure was unchanged by sitagliptin at rest and during exercise, but slightly lowered by voglibose at anaerobic threshold and peak exercise. In patients with T2DM and CAD, sitagliptin had little effect on resting LV and arterial function, exercise capacity, or exercise hemodynamics. Further studies need to be conducted with more patients as the number of the patients in this study was limited.

Comparison of non-exercise cardiorespiratory fitness prediction equations in apparently healthy adults.

Peterman JE; Whaley MH; Harber MP; Fleenor BS; Imboden MT; Myers J; Arena R; Kaminsky LA;

European Journal Of Preventive Cardiology [Eur J Prev Cardiol] 2019 Oct 22, pp. 2047487319881242. Date of Electronic Publication: 2019 Oct 22.

Aims: A recent scientific statement suggests clinicians should routinely assess cardiorespiratory fitness using at least non-exercise prediction equations. However, no study has comprehensively compared the many non-exercise cardiorespiratory fitness prediction equations to directly-measured cardiorespiratory fitness using data from a single cohort. Our purpose was to compare the accuracy of non-exercise prediction equations to directly-measured cardiorespiratory fitness and evaluate their ability to classify an individual’s cardiorespiratory fitness.
Methods: The sample included 2529 tests from apparently healthy adults (42% female, aged 45.4 ± 13.1 years (mean±standard deviation). Estimated cardiorespiratory fitness from 28 distinct non-exercise prediction equations was compared with directly-measured cardiorespiratory fitness, determined from a cardiopulmonary exercise test. Analysis included the Benjamini-Hochberg procedure to compare estimated cardiorespiratory fitness with directly-measured cardiorespiratory fitness, Pearson product moment correlations, standard error of estimate values, and the percentage of participants correctly placed into three fitness categories.
Results: All of the estimated cardiorespiratory fitness values from the equations were correlated to directly measured cardiorespiratory fitness (p < 0.001) although the R2 values ranged from 0.25-0.70 and the estimated cardiorespiratory fitness values from 27 out of 28 equations were statistically different compared with directly-measured cardiorespiratory fitness. The range of standard error of estimate values was 4.1-6.2 ml·kg-1·min-1. On average, only 52% of participants were correctly classified into the three fitness categories when using estimated cardiorespiratory fitness.
Conclusion: Differences exist between non-exercise prediction equations, which influences the accuracy of estimated cardiorespiratory fitness. The present analysis can assist researchers and clinicians with choosing a non-exercise prediction equation appropriate for epidemiological or population research. However, the error and misclassification associated with estimated cardiorespiratory fitness suggests future research is needed on the clinical utility of estimated cardiorespiratory fitness.