Author Archives: Paul Older

Impact of High Respiratory Exchange Ratio During Submaximal Exercise on Adverse Clinical Outcome in Heart Failure.

Kakutani N; Fukushima A; Yokota T; Katayama T; Nambu H; Shirakawa R; Maekawa S; Abe T; Takada S; Furihata T;Ono K; Okita K; Kinugawa S; Anzai T;

Circulation Journal: Official Journal Of The Japanese Circulation Society [Circ J] 2018 Aug 31. Date of Electronic Publication: 2018 Aug 31.

Background: Oxygen uptake (V̇O2) at peak workload and anaerobic threshold (AT) workload are often used for grading heart failure (HF) severity and predicting all-cause mortality. The clinical relevance of respiratory exchange ratio (RER) during exercise, however, is unknown.

Methods and Results: We retrospectively studied 295 HF patients (57±15 years, NYHA class I-III) who underwent cardiopulmonary exercise testing. RER was measured at rest; at AT workload; and at peak workload. Peak V̇O2had an inverse correlation with RER at AT workload (r=-0.256), but not at rest (r=-0.084) or at peak workload (r=0.090). Using median RER at AT workload, we divided the patients into high RER (≥0.97) and low RER (<0.97) groups. Patients with high RER at AT workload were characterized by older age, lower body mass index, anemia, and advanced NYHA class. After propensity score matching, peak V̇O2 tended to be lower in the high-RER than in the low-RER group (14.9±4.5 vs. 16.1±5.0 mL/kg/min, P=0.06). On Kaplan-Meier analysis, HF patients with a high RER at AT workload had significantly worse clinical outcomes, including all-cause mortality and rate of readmission due to HF worsening over 3 years (29% vs. 15%, P=0.01).
Conclusions: High RER during submaximal exercise, particularly at AT workload, is associated with poor clinical outcome in HF patients.

Peripheral endothelial function is positively associated with maximal aerobic capacity in patients with chronic obstructive pulmonary disease.

Vaes AW; Spruit MA; Theunis J; Wouters EFM; De Boever P;

Respiratory Medicine [Respir Med] 2018 Sep; Vol. 142, pp. 41-47. Date of Electronic Publication: 2018 Jul 21.

Background: Patients with COPD are frequently diagnosed with cardiovascular disease. Peripheral endothelial dysfunction is an underlying mechanism and can be used as an early marker of cardiovascular impairment. To date, little is known on the association between peripheral endothelial dysfunction, cardiovascular risk factors and measurements of exercise capacity in patients with COPD. Therefore, we aimed to determine the relation between endothelial function and patient characteristics, cardiovascular risk factors and (micro)vascular and functional performance in patient with CODP.
Methods: Clinical and demographic data of patients with COPD were measured during routine pre-rehabilitation assessment. Cardiovascular risk factors, including blood pressure, ankle brachial index, arterial stiffness and retinal vessel widths were obtained. Peripheral endothelial function was measured using the EndoPAT-2000. Functional performance was assessed using cardiopulmonary exercise test, constant work rate test and six-minute walk test.
Results: 40 patients with COPD completed the study protocol (65% males; mean age: 62.8 ± 7.3 years; mean FEV1: 45.8 ± 17.5 %pred). Peripheral endothelial dysfunction was observed in 55% of the patients. Patients with peripheral endothelial dysfunction had significantly worse aerobic exercise capacity and higher prevalence of cardiovascular risk factors. Stepwise multivariate regression models identified sex, systolic blood pressure and maximal aerobic capacity as independent correlates of peripheral endothelial function. After correction for sex, age and systolic blood pressure, there was a significant partial correlation between peripheral endothelial function and maximal aerobic capacity (R = 0.51, p = 0.004).
Conclusion: Peripheral endothelial function was positively associated with maximal aerobic capacity, when correcting for sex, age and systolic blood pressure. Establishing peripheral endothelial dysfunction as a determinant of impaired aerobic capacity in COPD can be valuable for developing interventions aiming to improve aerobic capacity, and in turn cardiovascular health.

The importance of right ventricular function in patients with pulmonary arterial hypertension.

Badagliacca R; Papa S; Poscia R; Pezzuto B; Manzi G; Torre R; Fedele F; Vizza CD;

Expert Review Of Respiratory Medicine [Expert Rev Respir Med] 2018 Sep 06, pp. 1-7. Date of Electronic Publication: 2018 Sep 06.

Introduction: Pulmonary arterial hypertension (PAH) is a progressive, life-threatening, and incurable disease. Its prognosis is based on right ventricular (RV) function. Therefore, adequate assessment of RV function is mandatory. Areas covered: This article presents the case of a patient with PAH in which the traditional diagnostic approach did not provide a complete assessment of RV function. The authors show how the analysis of other parameters yielded additional information that improved the management of this patient. Expert commentary: Despite current treatments, PAH often worsens due to progressive RV dysfunction. Appropriate assessment of RV function may facilitate the early identification of patients at risk of RV function impairment. More aggressive treatment of PAH might delay progression of the disease. Traditional risk stratification, which is based on New York Heart Association/World Health Organization (NYHA/WHO) functional class evaluation, the 6-minute walk test, and right heart catheterization, proves insufficient in many PAH patients, as it does not provide complete information about RV function. Thus, further parameters are required. Analysis of RV function, in addition to echocardiography and cardiopulmonary exercise testing, may add relevant prognostic information and improve therapy.

Step oximetry test: a validation study.

Fox BD; Sheffy N; Vainshelboim B; Fuks L; Kramer MR;

BMJ Open Respiratory Research [BMJ Open Respir Res] 2018 Aug 03; Vol. 5 (1), pp. e000320. Date of Electronic Publication: 20180803 (Print Publication: 2018).

Introduction: Step climbing is a potentially useful modality for testing exercise capacity. However, there are significant variations between test protocols and lack of consistent validation against gold standard cycle ergometry cardiopulmonary exercise testing (CPET). The purpose of the study was to validate a novel technique of exercise testing using a dedicated device.
Methods: We built a step oximetry device from an adapted aerobics step and pulse oximeter connected to a computer. Subjects performed lung function tests, a standard incremental cycle CPET and also a CPET while stepping on and off the step oximetry device to maximal exertion. Data from the step oximetry device were processed and correlated with standard measurements of pulmonary function and cycle CPET.
Results: We recruited 89 subjects (57 years, 50 men). Oxygen uptake (VO2) was 0.9 mL/kg/min (95% CI -3.6 to 5.4) higher in the step test compared with the gold standard cycle CPET, p<0.001. VO2 in the two techniques was highly correlated (R=0.87, p<0.001). Work rate during stair climbing showed the best correlation with VO2 (R=0.69, p<0.0001). Desaturation during step climbing correlated negatively with diffusion capacity for carbon monoxide (r=-0.43, p<0.005). No adverse events occurred.
Conclusions: The step oximetry test was a maximal test of exertion in the subjects studied, achieving slightly higher VO2 than during the standard test. The test was safe to perform and well tolerated by the patients. Parameters derived from the step oximetry device correlated well with gold standard measurements. The step oximetry test could become a useful and standardisable exercise test for clinical settings where advanced testing is not available or appropriate.

Feasibility of a home-based exercise intervention with remote guidance for patients with stable grade II and III gliomas: a pilot randomized controlled trial.

Gehring K, Kloek CJ, Aaronson NK, Janssen KW, Jones LW,
Sitskoorn MM, Stuiver MM

Clin Rehabil. 2018 Mar;32(3):352-366. doi: 10.1177/0269215517728326. Epub 2017
Sep 8.

OBJECTIVE: In this pilot study, we investigated the feasibility of a home-based,
remotely guided exercise intervention for patients with gliomas.
DESIGN: Pilot randomized controlled trial (RCT) with randomization (2:1) to
exercise or control group.
SUBJECTS: Patients with stable grade II and III gliomas.
INTERVENTION: The six-month intervention included three home-based exercise
sessions per week at 60%-85% of maximum heart rate. Participants wore heart rate
monitors connected to an online platform to record activities that were monitored
weekly by the physiotherapist.
MAIN MEASURES: Accrual, attrition, adherence, safety, satisfaction,
patient-reported physical activity, VO2 peak (by maximal cardiopulmonary exercise
testing) and body mass index (BMI) at baseline and at six-month follow-up.
RESULTS: In all, 34 of 136 eligible patients (25%) were randomized to exercise
training ( N = 23) or the control group ( N = 11), of whom 19 and 9,
respectively, underwent follow-up. Mean adherence to prescribed sessions was 79%.
Patients’ experiences were positive. There were no adverse events. Compared to
the control group, the exercise group showed larger improvements in absolute VO2
peak (+158.9 mL/min; 95% CI: -44.8 to 362.5) and BMI (-0.3 kg/m²; 95% CI: -0.9 to
0.2). The median increase in physical activity was 1489 metabolic equivalent of
task (MET) minutes higher in the exercise group. The most reported reasons for
non-participation were lack of motivation or time.
CONCLUSION: This innovative and intensive home-based exercise intervention was
feasible in a small subset of patients with stable gliomas who were interested in
exercising. The observed effects suggest that the programme may improve
cardiorespiratory fitness. These results support the need for large-scale trials
of exercise interventions in brain tumour patients.

The Impact of Bariatric Surgery on Cardiopulmonary Function: Analyzing VO2 Recovery Kinetics.

Remígio MI; Santa Cruz F; Ferraz Á; Remígio MC; Parente G; Nascimento I; Brandão D; Dornelas de Andrade AF;
de Moraes Neto F; Campos J;

Obesity Surgery [Obes Surg] 2018 Aug 15. Date of Electronic Publication: 2018 Aug 15.

Purpose: To assess cardiopulmonary capacity, autonomic heart function, and oxygen recovery kinetics during exercise testing before and after bariatric surgery.
Methods: This is a prospective cohort study. Symptom-limited cardiopulmonary exercise testing was performed with 24 patients, 1 week before and 4 months after bariatric surgery. The main variables were maximum oxygen uptake (VO2 max), the time elapsed until the appearance of the first ventilatory threshold (TLV1), and VO2 oxygen kinetics during recovery with a 50% reduction in peak oxygen uptake in the recovery period after exercise (50%VO2RP).
Results: The study demonstrated that the peak VO2\kg increased significantly after bariatric surgery. When analyzed without adjusting for weight, the peak VO2 paradoxically and significantly decreased after the surgical procedure (p = 0.007). The exercise time until the anaerobic threshold was longer after surgical procedure than before it (p = 0.001). Regarding post-exercise oxygen recovery kinetics, there was a faster reduction in the peak oxygen uptake after bariatric surgery than before the procedure (p < 0.001).
Conclusions: There was an obvious cardiac autonomic improvement after surgery. Despite the improvement in exercise tolerance, patients undergoing bariatric surgery had lower maximum oxygen consumption in the analysis not corrected for body weight. The mean VO2RP before bariatric surgery was 141 s and was 111 s after the surgical procedure (p < 0.001). These results suggest an improvement in the recovery kinetics of oxygen consumption, a novel index of cardiac reserve capacity, on patients undergoing bariatric surgery.

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease.

Lai S, Mastroluca D, Matino S, Panebianco V, Vitarelli A,
Capotosto L, Turinese I, Marinelli P, Rossetti M, Galani A,
Baiocchi P, D’Angelo AR, Palange P.

Kidney Blood Press Res. 2017;42(6):1290-1302. doi: 10.1159/000486011. Epub 2017
Dec 15.

BACKGROUND/AIMS: Cardiovascular disease is the most frequent cause of morbidity
and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients,
often before the onset of renal failure, and the pathogenetic mechanism is not
yet well elucidated. The aim of the study was to identify early and noninvasive
markers of cardiovascular risk in young ADPKD patients, in the early stages of
METHODS: A total of 26 patients with ADPKD and 24 control group, matched for age
and sex, were enrolled, and we have assessed inflammatory indexes, mineral
metabolism, metabolic state and markers of atherosclerosis and endothelial
dysfunction (carotid intima media thickness (IMT), ankle brachial index (ABI),
flow mediated dilation (FMD), renal resistive index (RRI), left ventricular mass
index (LVMI)) and cardiopulmonary exercise testing (CPET), maximal O2 uptake
(V’O2max), and O2 uptake at lactic acid threshold (V’O2@LT).
RESULTS: The ADPKD patients compared to control group, showed a significant
higher mean value of LVMI, RRI, homocysteine (Hcy), Homeostasis Model
Assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), Cardiac-troponinT
(cTnT) and intact parathyroid hormone (iPTH) (p<0.001, p<0.001, p<0.001, p<0.001,
p<0.001, p=0.007, p=0.019; respectively), and a lower value of FMD and
25-hydroxyvitaminD (25-OH-VitD) (p<0.001, p<0.001) with reduced parameters of
exercise tolerance, as V’O2max, V’O2max/Kg and V’O2max (% predicted) (p<0.001,
p<0.001, p=0.018; respectively), and metabolic response indexes (V’O2@LT, V’O2
@LT%, V’O2@LT/Kg,) (p<0.001, p=0.14, p<0.001; respectively). Moreover,
inflammatory indexes were significantly higher in ADPKD patients, and we found a
positive correlation between HOMA-IR and C-reactive protein (CRP) (r=0.507,
p=0.008), and a negative correlation between HOMA-IR and 25-OH-VitD (r=-0.585,
CONCLUSION: In our study, ADPKD patients, in the early stages of disease, showed
a greater insulin resistance, endothelial dysfunction, inflammation and mineral
metabolism disorders, respect to control group. Moreover, these patients
presented reduced tolerance to stress, and decreased anaerobic threshold to CPET.
Our results indicate a major and early cardiovascular risk in ADPKD patients.
Therefore early and noninvasive markers of cardiovascular risk and CPET should be
carried out, in ADPKD patients, in the early stages of disease, despite the cost

Dose-dependent efficacy of β-blocker in patients with chronic heart failure and atrial fibrillation.

Campodonico J; Piepoli M; Clemenza F; Bonomi A; Paolillo S; Salvioni E; Corrà U; Binno S; Veglia F; Lagioia R; Sinagra G; Cattadori G; Scardovi AB; Metra M; Senni M; Scrutinio D; Raimondo R; Emdin M; Magrì D; Parati G; Re F;Cicoira M; Minà C; Limongelli G; Correale M; Frigerio M; Bussotti M; Perna E; Battaia E; Guazzi M; Badagliacca R; DiLenarda A; Maggioni A; Passino C; Sciomer S; Pacileo G; Mapelli M; Vignati C; Lombardi C; Filardi PP; Agostoni P;

International Journal Of Cardiology [Int J Cardiol] 2018 Aug 06. Date of Electronic Publication: 2018 Aug 06.

Background: The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned.
Methods and Results: We analyzed data from HF patients (958 patients (801 males, 84%, age 67 ± 11 years)) with AF enrolled in the MECKI score database. We evaluated prognosis (composite of cardiovascular death, urgent heart transplant, or left ventricular assist device) of patients receiving β-blockers (n = 777, 81%) vs. those not treated with β-blockers (n = 181, 19%). We also analyzed the role β1-selectivity and the role of daily β-blocker dose. To account for different HF severity, Kaplan-Meier survival curves were normalized for relevant confounding factors and for treatment strategies. Dose was available in 629 patients. Median follow-up was 1312 (577-2304) days in the entire population, 1203 (614-2420) and 1325 (569-2300) days in patients not receiving and receiving β-blockers. 224 (23%, 54/1000 events/year), 163 (21%, 79/1000 events/year), and 61 (34%, 49/1000 events/year) events were recorded, respectively. At 10-year patients treated with β-blockers had a better outcome (HR 0.447, p < 0.01) with no effects as regards β1selective drugs (53%) vs. β1-β2 blockers (47%). Survival improved in parallel with β-blocker dose increase (HR 0.296, 0.496, 0.490 for the high, medium, and low dose vs. no β-blockers, p < 0.0001).
Conclusion: HF patients with AF taking a β-blocker have a better outcome (with a survival improvement in parallel with daily dose but no differences as regards β1 selectivity) but this does not mean that β-blockers improve outcomes in these patients as we cannot control for all the potential confounders associated with β-blocker use.

French Society of Cardiology guidelines on exercise tests (part 2): Indications for exercise tests in cardiac diseases.

Marcadet DM; Pavy B; Bosser G; Claudot F; Corone S; Douard H; Iliou MC; Amedro P; Le Tourneau T; Cueff C; Avedian T; Solal AC; Carré F;

Archives Of Cardiovascular Diseases [Arch Cardiovasc Dis] 2018 Aug 06. Date of Electronic Publication: 2018 Aug 06.

The exercise test is performed routinely in cardiology; its main indication is the diagnosis of myocardial ischemia, evaluated along with the subject’s pretest probability and cardiovascular risk level. Other criteria, such as analysis of repolarization, must be taken into consideration during the interpretation of an exercise test, to improve its predictive value. An exercise test is also indicated for many other cardiac diseases (e.g. rhythm and conduction disorders, severe asymptomatic aortic stenosis, hypertrophic cardiomyopathy, peripheral artery disease, hypertension). Moreover, an exercise test may be indicated for specific populations (women, the elderly, patients with diabetes mellitus, patients in a preoperative context, asymptomatic patients and patients with congenital heart defects). Some cardiac diseases (such as chronic heart failure or arterial pulmonary hypertension) require a cardiopulmonary exercise test. Finally, an exercise test or a cardiopulmonary exercise test is indicated to prescribe a cardiac rehabilitation programme, adapted to the patient.

French Society of Cardiology guidelines on exercise tests (part 1): Methods and interpretation.

Marcadet DM; Pavy B; Bosser G; Claudot F; Corone S; Douard H; Iliou MC; Vergès-Patois B; Amedro P; Le Tourneau T; Cueff C; Avedian T; Solal AC; Carré F;

Archives Of Cardiovascular Diseases [Arch Cardiovasc Dis] 2018 Aug 06. Date of Electronic Publication: 2018 Aug 06.

The exercise test is still a key examination in cardiology, used for the diagnosis of myocardial ischemia, as well as for the clinical evaluation of other heart diseases. The cardiopulmonary exercise test can further define functional capacity and prognosis for any given cardiac pathology. These new guidelines focus on methods, interpretation and indications for an exercise test or cardiopulmonary exercise test, as summarized below. The safety rules associated with the exercise test must be strictly observed. Interpretation of exercise tests and cardiopulmonary exercise tests must be multivariable. Functional capacity is a strong predictor of all-cause mortality and cardiovascular events. Chest pain, ST-segment changes and an abnormal ST/heart rate index constitute the first findings in favor of myocardial ischemia, mostly related to significant coronary artery disease. Chronotropic incompetence, abnormal heart rate recovery, QRS changes (such as enlargement or axial deviations) and the use of scores (based on the presence of various risk factors) must also be considered in exercise test interpretation for a coronary artery disease diagnosis. Arrhythmias or conduction disorders arising during the exercise test must be considered in the assessment of prognosis, in addition to a decrease or low increase in blood pressure during the exercise phase. When performing a cardiopulmonary exercise test, peak oxygen uptake and the volume of expired gas/carbon dioxide output slope are the two main variables used to evaluate prognosis.  [PART 2 FOLLOWS]