Category Archives: Publications

Two weeks of lower body resistance training enhances cycling tolerability to improve precision of maximal cardiopulmonary exercise testing in sedentary middle-aged females.

Wagoner CW; Hanson ED; Ryan ED; Brooks R; Wood WA; Jensen BC; Lee JT;
Coffman EM; Battaglini CL.

Applied Physiology, Nutrition, & Metabolism = Physiologie Appliquee,
Nutrition et Metabolisme. 44(11):1159-1164, 2019 Nov.
VI 1

It is not uncommon for sedentary individuals to cite leg fatigue as the
primary factor for test termination during a cardiopulmonary exercise test
(CPET) on a cycle ergometer. The purpose of this study was to examine the
effect of 2 weeks of lower body resistance training (RT) on
cardiopulmonary capacity in sedentary middle-aged females. Additionally,
the impact of RT on muscle strength was evaluated.
Following familiarization, 28 women (18 exercise group, 10 control group) completed
a maximal CPET on a cycle ergometer to determine peak oxygen uptake and
leg extensor strength assessed using isokinetic dynamometry. Participants
in the exercise group performed 2 weeks (6 sessions) of lower body RT,
which comprised leg press, leg curl, and leg extension exercises.
A 2-way repeated-measures ANOVA was used to evaluate the difference in changes of
peak oxygen uptake and peak torque (PT). Peak oxygen uptake significantly
improved from 22.2 +/- 4.5 to 24.3 +/- 4.4
(10.8%, p < 0.05) as well as PT from 83.1 +/- 25.4 Nm to 89.0 +/- 29.7 Nm
(6.1%, p < 0.05) in the exercise group with no change in the control
These findings provide initial evidence that 2 weeks of lower body
RT prior to a CPET may be a helpful preconditioning strategy to achieve a
more accurate peak oxygen uptake during testing, enhancing tolerability to
a CPET by improving lower body strength.

Pulse wave transit time during exercise testing reflects the severity of heart disease in cardiac patients.

Takayanagi Y; Koike A; Kubota H; Wu L; Nishi I; Sato A; Aonuma K; Kawakami
Y; Ieda M.

Drug Discoveries & Therapeutics. 14(1):21-26, 2020 Mar 08.
VI 1

The pulse wave transit time (PWTT) is easily measured as the time from the
R wave of an electrocardiogram to the arrival of the pulse wave measured
by an oxygen saturation monitor at the earlobe. We investigated whether
the change of PWTT during exercise testing reflects cardiopulmonary
function. Eighty-nine cardiac patients who underwent cardiopulmonary
exercise testing (CPX) were enrolled. We analyzed the change of PWTT
during exercise and the relationship between the shortening of the PWTT
and CPX parameters. PWTT was significantly shortened from rest to peak
exercise (204.6 +/- 33.6 vs. 145.6 +/- 26.4 msec, p < 0.001) in all of the
subjects. The patients with heart failure had significantly higher PWTT at
peak exercise than the patients without heart failure (152.7 +/- 27.1 vs.
140.4 +/- 24.8 msec, p = 0.031). The shortening of PWTT from rest to peak
exercise showed significant positive correlations with the peak O2 uptake
(VO2) (r = 0.56, p < 0.001), anaerobic threshold (r = 0.40, p = 0.016),
and % increase of systolic blood pressure during exercise (r = 0.75, p <
0.001), and a negative correlation with the slope of the increase in
ventilation versus the increase in CO2 output (VE-VCO2 slope) (r = – 0.42,
p = 0.010) in the patients with heart failure. PWTT was shortened during
exercise as the exercise intensity increased. In the patients with heart
failure, the shortening of PWTT from rest to peak exercise was smaller in
those with lower exercise capacity and those with higher VE-VCO2 slope, an
established index known to reflect the severity of heart failure.

Age- and gender-specific upper limits and reference equations for workload-indexed systolic blood pressure response during bicycle ergometry

Hedman, K; Lindow, T; Elmberg, V; Brudin, L; Ekstrom, M.

Eur J Prev Cardiol. 2020:2047487320909667.  Link to actual article.

BACKGROUND: Guidelines recommend considering workload in interpretation of the systolic blood pressure (SBP) response to exercise, but reference values are lacking.
DESIGN: This was a retrospective, consecutive cohort study.
METHODS: From 12,976 subjects aged 18-85 years who performed a bicycle ergometer exercise test at one centre in Sweden during the years 2005-2016, we excluded those with prevalent cardiovascular disease, comorbidities, cardiac risk factors or medications. We extracted SBP, heart rate and workload (watt) from >/= 3 time points from each test. The SBP/watt-slope and the SBP/watt-ratio at peak exercise were calculated. Age- and sex-specific mean values, standard deviations and 90th and 95th percentiles were determined. Reference equations for workload-indexed and peak SBP were derived using multiple linear regression analysis, including sex, age, workload, SBP at rest and anthropometric variables as predictors.
RESULTS: A final sample of 3839 healthy subjects (n = 1620 female) were included. While females had lower mean peak SBP than males (188 +/- 24 vs 202 +/- 22 mmHg, p < 0.001), workload-indexed SBP measures were markedly higher in females; SBP/watt-slope: 0.52 +/- 0.21 versus 0.41 +/- 0.15 mmHg/watt (p < 0.001); peak SBP/watt-ratio: 1.35 +/- 0.34 versus 0.90 +/- 0.21 mmHg/watt (p < 0.001). Age, sex, exercise capacity, resting SBP and height were significant predictors of the workload-indexed SBP parameters and were included in the reference equations. CONCLUSIONS: These novel reference values can aid clinicians and exercise physiologists in interpreting the SBP response to exercise and may provide a basis for future research on the prognostic impact of exercise SBP. In females, a markedly higher SBP in relation to workload could imply a greater peripheral vascular resistance during exercise than in males.

Atrial function in Fontan patients assessed by CMR: Relation with exercise capacity and long-term outcomes.

van der Ven JPG, Alsaied T, Juggan S, Bossers SSM, van den Bosch E, Kapusta L, Kuipers IM, Kroft LJM, Ten Harkel ADJ, van Iperen GG, Rathod RH, Helbing WA.

Int J Cardiol. 2020 Feb 24. pii: S0167-5273

OBJECTIVE: To assess the role of atrial function on exercise capacity and
clinical events in Fontan patients.
DESIGN: We included 96 Fontan patients from 6 tertiary centers, aged 12.8 (IQR
10.1-15.6) years, who underwent cardiac magnetic resonance imaging and
cardiopulmonary exercise testing within 12 months of each other from 2004 to
2017. Intra-atrial lateral tunnel (ILT) and extracardiac conduit (ECC) patients
were matched 1:1 with regard to age, gender and dominant ventricle. The pulmonary
venous atrium was manually segmented in all phases and slices. Atrial function
was assessed by volume-time curves. Furthermore, atrial longitudinal and
circumferential feature tracking strain was assessed. We determined the relation
between atrial function and exercise capacity, assessed by peak oxygen uptake and
VE/VCO2 slope, and events (mortality, listing for transplant, re-intervention,
arrhythmia) during follow-up.
RESULTS: Atrial maximal and minimal volumes did not differ between ILT and ECC
patients. ECC patients had higher reservoir function (21.1 [16.4-28.0]% vs 18.2
[10.9-22.2]%, p = .03), lower conduit function and lower total circumferential
strain (13.8 ± 5.1% vs 18.0 ± 8.7%, p = .01), compared to ILT patients. Only for
ECC patients, a better late peak circumferential strain rate predicted better
VE/VCO2 slope. No other parameter of atrial function predicted peak oxygen uptake
or VE/VCO2 slope. During a median follow-up of 6.2 years, 42 patients reached the
composite end-point. No atrial function parameters predicted events during
CONCLUSIONS: ECC patients have higher atrial reservoir function and lower conduit
function. Atrial function did not predict exercise capacity or events during

Inspiratory muscle training did not improve exercise capacity and lung function in adult patients with Fontan circulation: A randomized controlled trial

Fritz C; Muller J; Oberhoffer R; Ewert P; Hager A


Patients with Fontan circulation have no subpulmonary ventricle and a passive pulmonary perfusion. Considerable percentage of the pulmonary blood flow is driven by pressure shift due to respiration. Impairments in respiratory musculature strength are associated with a reduced exercise capacity. This study investigated the effect of a daily six months inspiratory muscle training (IMT) on exercise and lung capacity in adult Fontan patients.

After a lung function and cardiopulmonary exercise test (CPET), 42 Fontan patients (50% female; 30.5 ± 8.1 years) were randomized into either an intervention group (IG), or a control group (CG). The IG performed a telephone-supervised, daily IMT of three sets with 10–30 repetitions for six months.


After six months of IMT, the IG did not improve in any exercise and lung capacity parameter compared to CG. VO2peak (ΔVO2peak: IG: 0.05 [−1.53; 1.33] ml/kg/min vs. CG: −0.50 [−1.20; 0.78] ml/kg/min; p = .784) and FVC (ΔFVC: IG: 0.07 [−0.16; 0.22] l vs. CG:−0.05 [−0.24; 0.18] l; p = .377) remained unchanged, while FEV1 trended to improve (ΔFEV1: IG: 0.05 [−0.07; 0.13] l vs. CG: −0.10 [−0.19; 0.03] l; p = .082). Only oxygen saturation at rest improved significantly (ΔSpO2: IG: 1.50 [−0.25; 3.00] % vs. CG: −0.50 [−1.75; 0.75] %; p = .017).

A daily six months IMT did not improve exercise and lung capacity and lung volumes in Fontan patients.

Beta-blockers withdrawal in patients with heart failure with preserved ejection fraction and chronotropic incompetence: Effect on functional capacity rationale and study design of a prospective, randomized, controlled trial (The Preserve-HR trial).

Palau P; Seller J; Domínguez E; Gómez I; Ramón JM; Sastre C; de la Espriella R; Santas E; Miñana G; Chorro FJ; González-Juanatey JR; Núñez J;

Clinical Cardiology [Clin Cardiol] 2020 Feb 19. Date of Electronic Publication: 2020 Feb 19.

Background: The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex and multifactorial. Chronotropic incompetence (ChI) has emerged as a crucial pathophysiological mechanism. Beta-blockers, drugs with negative chronotropic effects, are commonly used in HFpEF, although current evidence does not support its routine use in these patients.
Hypothesis: We postulate beta-blockers may have deleterious effects in HFpEF and ChI. This work aims to evaluate the short-term effect of beta-blockers withdrawal on functional capacity assessed by the maximal oxygen uptake (peakVO2) in patients with HFpEF and ChI.
Methods: This is a prospective, crossover, randomized (1:1) and multicenter study. After randomization, the clinical and cardiac rhythm will be continuously registered for 30 days. PeakVO2 is assessed by cardiopulmonary exercise testing (CPET) at 15 and 30 days in both groups. Secondary endpoints include quality of life, cognitive, and safety assessment. Patients with stable HFpEF, functional class New York Heart Association (NYHA) II-III, chronic treatment with beta-blockers, and ChI will be enrolled. A sample size estimation [alfa: 0.05, power: 90%, a 20% loss rate, and delta change of mean peakVO2: +1.2 mL/kg/min (SD ± 2.0)] of 52 patients is necessary to test our hypothesis.
Results: Patients started enrolling in October 2018. As January 14th, 2020, 28 patients have been enrolled. It is projected to enroll the last patient at the end of July 2020.
Conclusions: Optimizing therapy that improves functional capacity remains an unmeet priority in HFpEF. Deprescribing beta-blockers in patients with HFpEF and ChI seems a plausible intervention to improve functional capacity. This trial is an attempt towards precision medicine in this complex syndrome.
Trial Registration: NCT03871803.

Effects of aerobic and anaerobic exercise on glucose tolerance in patients with coronary heart disease and type 2 diabetes mellitus.

Schwaab B; Kafsack F; Markmann E; Schütt M;

Cardiovascular Endocrinology & Metabolism [Cardiovasc Endocrinol Metab] 2020 Feb 21; Vol. 9 (1), pp. 3-8. Date of Electronic Publication: 20200221 (Print Publication: 2020).

In patients with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM), physical activity is strongly advised as nonpharmacological therapy. In general, a moderate aerobic exercise intensity is recommended. It was also proposed, however, that greater intensities tend to yield even greater benefits in HbA1c. Hence, the most appropriate exercise intensity seems not to be established yet. We compared the effect of moderate (aerobic) and vigorous (anaerobic) activity on postprandial plasma glucose.
Methods: In 10 consecutive patients (63 ± 12 years, BMI 28.3 ± 2.6 kg/m2, fasting plasma glucose 6.1 ± 1.2 mmol/l), 2-hour plasma glucose was ≥11.1 mmol/l in the oral glucose tolerance test at rest (OGTT-0). Cardiopulmonary exercise test (CPX) was performed until a respiratory exchange ratio (RER) ≥1.20, beeing anaerobic (CPX-1), followed by OGTT-1. A steady-state CPX of 30-minute duration was performed targeting an RER between 0.90 and 0.95, being aerobic (CPX-2), followed by OGTT-2.
Results: In CPX-1, maximum exercise intensity (maxIntensity) averaged at 99 ± 30 Watt and peak oxygen consumption (VO2peak) reached 15.9 ± 2.8 ml/min/kg. In CPX-2, aerobic intensity averaged at 29 ± 9 Watt, representing 31% of maxIntensity and 61% of VO2peak. After aerobic exercise, 2-hour plasma glucose was significantly reduced to an average of 9.4 ± 2.3 mmol/l (P < 0.05). Anaerobic exercise did not reduce 2-hour plasma glucose as compared to OGTT-0 (12.6 ± 2.2 vs 12.6 ± 3.9 mmol/l).
Conclusion: Aerobic exercise intensity was very low in our patients with CHD and T2DM. Postprandial plasma glucose was reduced only by aerobic exercise. Larger studies on the optimal exercise intensity are needed in this patient cohort.

Coronary sinus Reducer implantation results in improved oxygen kinetics at cardiopulmonary exercise test in patients with refractory angina.

Zivelonghi C; Konigstein M; Azzano A; Agostoni P; Topilski Y; Banai S; Verheye S

Eurointervention: Journal Of Europcr In Collaboration With The Working Group On Interventional Cardiology Of The European Society Of Cardiology [EuroIntervention] 2020 Feb 25. Date of Electronic Publication: 2020 Feb 25.

Aims: Refractory angina is still a major public health problem. The Coronary Sinus Reducer (CSR) has recently been introduced as an alternative treatment to reduce symptoms in these patients. Aim of this study is to investigate objective improvements in effort tolerance and oxygen kinetics as assessed by cardiopulmonary exercise testing (CPET) in patients suffering from refractory angina undergoing CSR implantation.
Methods and Results: In this multicentre prospective study, patients with chronic refractory angina undergoing CSR implantation were scheduled for CPET before the index procedure and at 6-month follow-up. Main endpoints of this analysis were improvements in VO 2 max and in VO 2 at anaerobic threshold (AT). Clinical events and improvements in symptoms were also recorded. A total of 37 patients formed the study population. CSR implantation procedure was successful and without complications in all. At follow-up CPET significant improvement in VO 2 max (+0.97 ml/kg/min [+11.3%], 12.2±3.6 ml/kg/min at baseline vs 13.2±3.7 ml/kg/min, p=0.026), and workload (+12.9[+34%]; 68±28 W vs 81±49W, p=0.05) were observed, with non-significant differences in VO 2 at AT (9.84±3.4 ml/kg/min vs 10.74±3.05 ml/kg/min, p=0.06). Canadian Cardiovascular Society (CCS) grade improved from a mean of 3.2±0.5 to 1.6±0.8 (p<0.01), and significant benefits in all Seattle Angina Questionnaire variables were shown.
Conclusions: In patients with obstructive coronary artery disease suffering from refractory angina, the implantation of CSR was associated with objective improvement in exercise capacity and oxygen kinetics at CPET, suggesting a possible reduction of myocardial ischemia.

Clinical implications of idiopathic pulmonary arterial hypertension phenotypes defined by cluster analysis.

Badagliacca R; Rischard F; Papa S; Kubba S; Vanderpool R;Yuan JX; Garcia JGN; Airhart S; Poscia R; Pezzuto B; DManzi G; Miotti C; Luongo F; Scoccia G; Torre Rn Msn R;Fedele F; Vizza CD;

The Journal Of Heart And Lung Transplantation: The Official Publication Of The International Society For Heart Transplantation [J Heart Lung Transplant] 2020 Jan 21. Date of Electronic Publication: 2020 Jan 21.

Background: Despite advances in drug development, life expectancy in idiopathic pulmonary arterial hypertension (IPAH) remains unacceptable. Contemporary IPAH characterization is based on criteria that may not adequately capture disease heterogeneity and may be proposed as a possible explanation for why patient outcome is still unfavorable. The aim of this study was to apply cluster analysis to improve phenotyping of patients with IPAH and analyze long-term clinical outcome of derived clusters.
Methods: Patients with IPAH from 2 referral centers (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Patients were classified according to cluster analysis and followed for clinical worsening occurrence.
Results: The cluster analysis identified 4 IPAH phenotypes. Cluster 1 was characterized by young patients, mild pulmonary hypertension (PH), mild right ventricular (RV) dilation and high oxygen (O2) pulse; Cluster 2 by severe PH and RV dilation and high O2 pulse; and Cluster 3 by male patients, severe PH and RV dilation, and low O2 pulse. Cluster 4 patients were older and overweight, with mild PH and RV dilation and low O2 pulse. After a mean follow-up of 995 ± 623 days, 123 (48.8%) patients had clinical worsening. Cluster 1 patients presented the best prognosis, whereas Cluster 3 had the highest rates of clinical worsening. Compared with Cluster 1, risk of clinical worsening ranged from 4.12 (confidence interval [CI] 1.43-11.92; p = 0.009) for Cluster 4 to 7.38 (CI 2.80-19.40) for Cluster 2 and 13.8 (CI 5.60-34.0; p = 0.0001) for Cluster 3.
Conclusions: Cluster analysis of clinical variables identified 4 distinct phenotypes of IPAH. Our findings underscore the high degree of disease heterogeneity that exists within patients with IPAH and the need for advanced clinical testing to define phenotypes to improve treatment strategy decision-making. CONDENSED ABSTRACT Idiopathic pulmonary arterial hypertension (IPAH) characterization is based on criteria that may not adequately capture disease heterogeneity. The aim of this study was to apply cluster analysis to improve phenotyping of IPAH. Patients with IPAH (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Within the umbrella category of IPAH, it was the combination of mean pulmonary arterial pressure, right ventricular size, and oxygen pulse that further stratified patients into novel IPAH phenotypes that significantly associate with clinical worsening. These findings underscore the need for novel multidimensional IPAH phenotyping for improved patient care and trial quality.