Category Archives: Publications

Association between skeletal muscle mass and cardiorespiratory fitness in community-dwelling elderly men.

Boo SH; Joo MC; Lee JM; Kim SC; Yu YM; Kim MS

Aging Clinical And Experimental Research [Aging Clin Exp Res] 2018 Jun 18. Date of Electronic Publication: 2018 Jun 18.

Background: Sarcopenia reduces physical ability and cardiorespiratory fitness (CRF), leading to poor quality of life.
Aim: The aim of this study was to investigate the relationship between skeletal muscle mass and CRF in elderly men.
Methods: We assessed 102 community-dwelling men over 60 years old. Appendicular skeletal muscle mass (ASM) was determined using bioelectrical impedance analysis, and the skeletal muscle mass index (SMI) was calculated as ASM divided by the square of height. Subjects with an SMI less than 7.0 kg/m2 were included in the sarcopenic group, as recommended by the Asian Working Group for Sarcopenia. To investigate CRF parameters, a cardiopulmonary exercise test was performed using the Bruce protocol. CRF parameters were subdivided into aerobic capacity, cardiovascular response, and ventilatory response.
Results: Of the 102 subjects, 15 (14.7%) were included in the sarcopenic group. There were significant correlations between SMI and peak oxygen consumption (VO2peak) (r = 0.597, p < 0.001), and between SMI and VO2peak/weight (r = 0.268, p = 0.024). Moreover, there were positive correlations between SMI and first ventilatory threshold (VT1) (r = 0.352, p = 0.008) and between SMI and VT1/weight (r = 0.189, p = 0.039). Additionally, peak oxygen pulse (O2pulsepeak) was significantly correlated with SMI (r = 0.558, p < 0.001). VO2peak, VO2peak/weight and O2pulsepeak showed significant differences between the sarcopenic and non-sarcopenic groups (p < 0.05, all). In multiple linear regression analyses, the factor related to VO2peak was SMI (β = 0.473, p < 0.001) and that related to O2pulsepeak was also SMI (β = 0.442, p < 0.001).
Discussion and Conclusions: This study demonstrated that skeletal muscle mass might be closely associated with CRF. Therefore, sarcopenia should be appropriately managed to improve an individual’s CRF.


A method for predicting peak work rate for cycle ergometer and treadmill ramp tests.

Saengsuwan J, Nef T, Hunt KJ.

Clin Physiol Funct Imaging. 2017 Nov;37(6):610-614.

BACKGROUND: Prediction of peak work rate (WRpeak) for incremental exercise
testing (IET) is important to bring subjects to their maximal performance within
the recommended 8-12 min. This study developed a novel method for prediction of
WRpeak for IET on cycles and treadmills.
METHODS: Peak metabolic equivalent of task (METpred) was predicted based on an
existing non-exercise prediction formula, and then, predicted peak work rate
(WRpred) was derived from separate formulae for the cycle and the treadmill.
Eighteen healthy subjects were included.
RESULTS: In males, there was no difference between WRpred versus WRpeak for both
the cycle ergometer (277·7 versus 275·6 W, P = 0·70) and the treadmill (264·1
versus 260·5, P = 0·58). In females, there was no difference between WRpred
versus WRpeak for the cycle ergometer (187·1 versus 188·3 W, P = 0·90), but a
significant difference was found between WRpred versus WRpeak on the treadmill
(178·6 versus 151·9 W, P<0·05). For males, the mean absolute percentage errors
for WRpred versus WRpeak were 4·6% and 5·7% for the cycle and treadmill,
respectively. For females, the errors were 12·2% and 20·8%. The algorithm was
successful in achieving the required duration of 8-12 min in 33 of 36 cases.
CONCLUSIONS: The peak work rate prediction protocol was accurate in male subjects
for both the cycle and the treadmill. In female subjects, the method was accurate
for the cycle, but systematically overpredicted the peak work rate on the
treadmill. The protocol requires further adaptation for females on the treadmill.

Reevaluating Modality of Cardiopulmonary Exercise Testing in Patients with Heart Failure and Resynchronization Therapy: Relevance of Heart Rate-Adaptive Pacing.

Goldraich L, Ross HJ, Foroutan F, Walker M, Braga J, McDonald

J Card Fail. 2017 May;23(5):422-426.

BACKGROUND: Chronotropic incompetence (CI) in heart failure (HF) patients with
cardiac resynchronization therapy (CRT) and activity sensors may vary according
to exercise modality. We hypothesized that chronotropic response and exercise
capacity differ when HF patients with CRT and heart rate (HR) adaptive pacing are
exercised on cycloergometer versus treadmill.
METHODS AND RESULTS: This is a crossover study in which stable HF patients with
CRT and HR-adaptive pacing triggered by activity sensors underwent maximal
symptom-limited cardiopulmonary exercise testing on both a cycloergometer and
treadmill. Adjusted percent of HR reserve (%HRR) was calculated as
HRR/age-predicted HRR. CI was defined as ≤62% of age-predicted HRR. Among 16
patients (59 ± 10 years, ejection fraction 27 ± 12%, 87% on beta-blockers),
prevalence of CI was high irrespective of exercise modality (87.5% on
cycloergometer vs 62.5% on treadmill; P = .12). Chronotropic responses were
better on the treadmill; %HRR was higher on a treadmill vs cycloergometer
(61 ± 26% vs 22 ± 31%; P = .003). Peak oxygen consumption was increased by 24% on
a treadmill vs cycloergometer (15.8 vs 12.7 mL/kg/min; P < .0001).
CONCLUSIONS: In HF patients with CRT and HR-adaptive pacing, treadmill
cardiopulmonary exercise testing enhances chronotropic response, HRR, and peak
oxygen consumption compared with a cycloergometer. These findings may have
implications in exercise prescription and thresholds for advanced therapies such
as heart transplantation and ventricular assist devices.

Cardiorespiratory optimal point during exercise testing as a predictor of all-cause mortality.

Ramos PS, Araújo CG

Rev Port Cardiol. 2017 Apr;36(4):261-269. doi: 10.1016/j.repc.2016.09.017. Epub
2017 Mar 17

INTRODUCTION AND AIM: The cardiorespiratory optimal point (COP) is a novel index,
calculated as the minimum oxygen ventilatory equivalent (VE/VO2) obtained during
cardiopulmonary exercise testing (CPET). In this study we demonstrate the
prognostic value of COP both independently and in combination with maximum oxygen
consumption (VO2max) in community-dwelling adults.
METHODS: Maximal cycle ergometer CPET was performed in 3331 adults (66% men) aged
40-85 years, healthy (18%) or with chronic disease (81%). COP cut-off values of
<22, 22-30, and >30 were selected based on the log-rank test. Risk discrimination
was assessed using COP as an independent predictor and combined with VO2max.
RESULTS: Median follow-up was 6.4 years (7.1% mortality). Subjects with COP >30
demonstrated increased mortality compared to those with COP <22 (hazard ratio
[HR] 6.86, 95% confidence interval [CI] 3.69-12.75, p<0.001). Multivariate
analysis including gender, age, body mass index, and the forced expiratory volume
in 1 s/vital capacity ratio showed adjusted HR for COP >30 of 3.72 (95% CI
1.98-6.98; p<0.001) and for COP 22-30 of 2.15 (95% CI 1.15-4.03, p<0.001).
Combining COP and VO2max data further enhanced risk discrimination.
CONCLUSIONS: COP >30, either independently or in combination with low VO2max, is
a good predictor of all-cause mortality in community-dwelling adults (healthy or
with chronic disease). COP is a submaximal prognostic index that is simple to
obtain and adds to CPET assessment, especially for adults unable or unwilling to
achieve maximal exercise.

Exercise training in Diastolic Heart Failure (Ex-DHF): rationale and design of a multicentre, prospective, randomized, controlled, parallel group trial.

Edelmann F, Bobenko A, Gelbrich G, Hasenfuss G,
Herrmann-Lingen C, Duvinage A, Schwarz S, Mende M, Prettin C,
Trippel T, Lindhorst R, Morris D, Pieske-Kraigher E, Nolte
K, Düngen HD, Wachter R, Halle M, Pieske B.

Eur J Heart Fail. 2017 Aug;19(8):1067-1074. doi: 10.1002/ejhf.862. Epub 2017 May

Heart failure with preserved ejection fraction (HFpEF) is a common disease with
high incidence and increasing prevalence. Patients suffer from functional
limitation, poor health-related quality of life, and reduced prognosis. A pilot
study in a smaller group of HFpEF patients showed that structured, supervised
exercise training (ET) improves maximal exercise capacity, diastolic function,
and physical quality of life. However, the long-term effects of ET on
patient-related outcomes remain unclear in HFpEF. The primary objective of the
Exercise training in Diastolic Heart Failure (Ex-DHF) trial is to investigate
whether a 12 month supervised ET can improve a clinically meaningful composite
outcome score in HFpEF patients. Components of the outcome score are all-cause
mortality, hospitalizations, NYHA functional class, global self-rated health,
maximal exercise capacity, and diastolic function. After undergoing baseline
assessments to determine whether ET can be performed safely, 320 patients at 11
trial sites with stable HFpEF are randomized 1:1 to supervised ET in addition to
usual care or to usual care alone. Patients randomized to ET perform supervised
endurance/resistance ET (3 times/week at a certified training centre) for 12
months. At baseline and during follow-up, anthropometry, echocardiography,
cardiopulmonary exercise testing, and health-related quality of life evaluation
are performed. Blood samples are collected to examine various biomarkers. Overall
physical activity, training sessions, and adherence are monitored and documented
throughout the study using patient diaries, heart rate monitors, and
accelerometers. The Ex-DHF trial is the first multicentre trial to assess the
long-term effects of a supervised ET programme on different outcome measures in
patients with HFpEF.

Stress hormones at rest and following exercise testing predict coronary artery disease severity and outcome

Popovic D, Damjanovic S, Djordjevic T, Martic D, Ignjatovic S,
Milinkovic N, Banovic M, Lasica R, Petrovic M, Guazzi M, Arena

Stress. 2017 Sep;20(5):523-531.

OBJECTIVES: Despite considerable knowledge regarding the importance of stress in
coronary artery disease (CAD) pathogenesis, its underestimation persists in
routine clinical practice, in part attributable to lack of a standardized,
objective assessment. The current study examined the ability of stress hormones
to predict CAD severity and prognosis at basal conditions as well as during and
following an exertional stimulus.
MATERIALS AND METHODS: Forty Caucasian subjects with significant coronary artery
lesions (≥50%) were included. Within 2 months of coronary angiography,
cardiopulmonary exercise testing (CPET) on a recumbent ergometer was performed in
conjunction with stress echocardiography (SE). At rest, peak and after 3 min of
recovery following CPET, plasma levels of cortisol, adrenocorticotropic hormone
(ACTH) and NT-pro-brain natriuretic peptide (NT-pro-BNP) were measured by
immunoassay sandwich technique, radioimmunoassay, and radioimmunometric
technique, respectively. Subjects were subsequently followed a mean of
32 ± 10 months.
RESULTS AND DISCUSSION: Mean ejection fraction was 56.7 ± 9.6%. Subjects with 1-2
stenotic coronary arteries (SCA) demonstrated a significantly lower plasma
cortisol levels during CPET compared to those with 3-SCA (p < .05), whereas ACTH
and NT-pro-BNP were not significantly different (p > .05). Among CPET, SE, and
hormonal parameters, cortisol at rest and during CPET recovery demonstrated the
best predictive value in distinguishing between 1-, 2-, and 3-SCA [area under ROC
curve 0.75 and 0.77 (SE = 0.11, 0.10; p = .043, .04) for rest and recovery,
respectively]. ΔCortisol peak/rest predicted cumulative cardiac events (area
under ROC curve 0.75, SE = 0.10, p = .049).
CONCLUSIONS: Cortisol at rest and following an exercise test holds predictive
value for CAD severity and prognosis, further demonstrating a link between stress
and unwanted cardiac events.

Outcome after Turndown for Elective Abdominal Aortic Aneurysm Surgery.

Whittaker JD, Meecham L, Summerour V, Khalil S, Layton G, Yousif
M, Jennings A, Wall M, Newman J

Eur J Vasc Endovasc Surg. 2017 Nov;54(5):579-586. doi:

OBJECTIVES: The aim was to assess the survival of patients who had been turned
down for repair of an abdominal aortic aneurysm (AAA) and to examine the factors
influencing this.
METHODS: This was a retrospective observational study of a prospectively
maintained database of all patients turned down for AAA intervention by the Black
Country Vascular Network multidisciplinary team (MDT) from January 2013 to
December 2015. Data on AAA size, cardiopulmonary exercise testing (CPET) and
cause of death were recorded.
RESULTS: There were 112 patients. The median age at turndown was 83.9 years (IQR
10.2 years). The median AAA size at turndown was 63 mm (IQR 16.7 mm). The median
follow-up time after turndown was 324 days (IQR 537.5 days). Sixty-four patients
(57.1%) were deceased after 2 years, with a median survival time of 462 days (IQR
579 days). Patients who died had a significantly larger AAA dimension (median
65 mm, IQR 18.5 mm) than those surviving to date (median 59 mm, IQR 10 mm,
p = .004). Using Cox regression analysis, the probability of 1 year survival in
the whole population was 0.614. The probability of 2 year survival was 0.388.
When accounting for age, gender, AAA dimension, and British Aneurysm Repair risk
score, no factors had significant influence over survival. Of the 64 deceased
patients, 30 had an accessible cause of death: 36.7% of these were due to
ruptured AAAs. There was no significant difference in AAA size between those
dying of ruptures and those dying of other causes (p = .225, mean 74 mm and 67 mm
CONCLUSIONS: Being turned down for AAA repair carries a significant short-term
risk of mortality. Those turned down for repair carried significant levels of
comorbid disease but no factors considered were found to be independently
predictive of the length of survival.

Comment in
Eur J Vasc Endovasc Surg. 2017 Nov;54(5):587

“There will inevitably be heterogeneity between institutions in terms of fitness threshold levels for offering abdominal aortic aneurysm (AAA) repair. If the threshold is set too high, there is a risk of denying a proportion of patients who would have otherwise potentially benefited from repair and had their AAA rupture prevented. If the threshold is set too low, this may result in high peri-operative mortality, and in the longer term, lower overall life expectancy among those repaired which will negate any long-term benefit from AAA repair………”

Home-based interval training increases endurance capacity in adults with complex congenital heart disease.

Sandberg C, Hedström M, Wadell K, Dellborg M, Ahnfelt A,
Zetterström AK, Öhrn A, Johansson B.

Congenit Heart Dis. 2018 Mar;13(2):254-262.

OBJECTIVE: The beneficial effects of exercise training in acquired heart failure
and coronary artery disease are well known and have been implemented in current
treatment guidelines. Knowledge on appropriate exercise training regimes for
adults with congenital heart disease is limited, thus further studies are needed.
The aim of this study was to examine the effect of home-based interval exercise
training on maximal endurance capacity and peak exercise capacity.
DESIGN: Randomized controlled trial.
METHODS: Twenty-six adults with complex congenital heart disease were recruited
from specialized units for adult congenital heart disease. Patients were
randomized to either an intervention group-12 weeks of home-based interval
exercise training on a cycle ergometer (n = 16), or a control group (n = 10). The
latter was instructed to maintain their habitual physical activities. An
incremental cardiopulmonary exercise test and a constant work rate
cardiopulmonary exercise test at 75% of peak workload were performed
preintervention and postintervention.
RESULTS: Twenty-three patients completed the protocol and were followed
(intervention n = 13, control n = 10). Postintervention exercise time at constant
work rate cardiopulmonary exercise test increased in the intervention group
compared to controls (median[range] 12[-4 to 52]min vs 0[-4 to 5]min, P = .001).
At incremental cardiopulmonary exercise test, peak VO2 increased 15% within the
intervention group (P = .019) compared to 2% within the control group (P = .8).
However, in comparison between the groups no difference was found (285[-200 to
535] ml/min vs 17[-380 to 306] ml/min, P = .10). In addition, peak workload at
incremental cardiopulmonary exercise test increased in the intervention group
compared to controls (20[-10 to 70]W vs 0[-20 to 15]W, P = .003).
CONCLUSION: Home-based interval exercise training increased endurance capacity
and peak exercise capacity in adults with complex congenital heart disease.
Aerobic endurance might be more relevant than peak oxygen uptake with regard to
daily activities, and therefore a more clinically relevant measure to evaluate.

Exercise gas exchange in continuous-flow left ventricular assist device recipients.

Mezzani A; Pistono M; Agostoni P; Giordano A; Gnemmi M; Imparato A; Temporelli P; Corrà U;

Plos One [PLoS One] 2018 Jun 01; Vol. 13 (6), pp. e0187112. Date of Electronic Publication: 20180601 (Print Publication: 2018)

Exercise ventilation/perfusion matching in continuous-flow left ventricular assist device recipients (LVAD) has not been studied systematically. Twenty-five LVAD and two groups of 15 reduced ejection fraction chronic heart failure (HFrEF) patients with peak VO2 matched to that of LVAD (HFrEF-matched) and ≥14 ml/kg/min (HFrEF≥14), respectively, underwent cardiopulmonary exercise testing with arterial blood gas analysis, echocardiogram and venous blood sampling for renal function evaluation. Arterial-end-tidal PCO2 difference (P(a-ET)CO2) and physiological dead space-tidal volume ratio (VD/VT) were used as descriptors of alveolar and total wasted ventilation, respectively. Tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio (TAPSE/PASP) and blood urea nitrogen/creatinine ratio were calculated in all patients and used as surrogates of right ventriculo-arterial coupling and circulating effective volume, respectively. LVAD and HFrEF-matched showed no rest-to-peak change of P(a-ET)CO2 (4.5±2.4 vs. 4.3±2.2 mm Hg and 4.1±1.4 vs. 3.8±2.5 mm Hg, respectively, both p >0.40), whereas a decrease was observed in HFrEF≥14 (6.5±3.6 vs. 2.8±2.0 mm Hg, p <0.0001). Rest-to-peak changes of P(a-ET)CO2 correlated to those of VD/VT (r = 0.70, p <0.0001). Multiple regression indicated TAPSE/PASP and blood urea nitrogen/creatinine ratio as independent predictors of peak P(a-ET)CO2. LVAD exercise gas exchange is characterized by alveolar wasted ventilation, i.e. hypoperfusion of ventilated alveoli, similar to that of advanced HFrEF patients and related to surrogates of right ventriculo-arterial coupling and circulating effective volume.

Sex-specific cardiopulmonary exercise testing parameters as predictors in patients with idiopathic pulmonary arterial hypertension

Yuan P, Ni HJ, Chen TX, Pudasaini B, Jiang R, Liu H, Zhao
QH, Wang L, Gong SG, Liu JM

Hypertens Res. 2017 Oct 5;40(10):868-875. doi: 10.1038/hr.2017.52. Epub 2017 Jun

Cardiopulmonary exercise testing (CPET) has been used for prognosis in idiopathic
pulmonary arterial hypertension (IPAH). We explored whether sex differences had
an impact on prognostic assessments of CPET in IPAH. Data were retrieved from 21
male and 36 female incident IPAH patients who underwent both right heart
catheterization and CPET from 2010 to 2016 at Shanghai Pulmonary Hospital. Cox
proportional hazards analysis was used to assess the prognostic value of CPET.
The mean duration of follow-up was 22±15 months. Nine men and 15 women had an
event. The differences in clinical parameters in the whole population were not
the same as the inter-subgroup differences. Event-free women had significantly
higher cardiac output, lower pulmonary vascular resistance and percentage of
predicted FVC compared with event men (all P<0.05). Event-free men had
significantly higher end-tidal partial pressure of CO2 (PETCO2) at anaerobic
threshold (AT), peak workload, PETCO2, maximum oxygen consumption (VO2)/minute
ventilation (VE), and oxygen uptake efficiency slope and lower end-tidal partial
pressure of O2 (PETO2) at AT, peak PETO2, and lowest VE/VCO2 compared with event
men. Event-free women had dramatically higher peak VO2, VCO2, VE and O2 pulse
than event women (all P<0.05). Peak PETCO2 was the independent predictor of
event-free survival in all patients and males, whereas peak O2 pulse was the
independent predictor of event-free survival in females. Men with peak
PETCO2⩾20.50 mm Hg, women with peak O2 pulse ⩾6.25 ml per beat and all patients
with peak PETCO2⩾27.03 mm Hg had significantly better event-free survival.
Sex-specific CPET parameters are predictors of poor outcomes. Decreased peak
PETCO2 in men and peak O2 pulse in women were associated with lower event-free
survival in IPAH.