Category Archives: Publications

Characteristics of cardiopulmonary exercise testing of patients with borderline mean pulmonary artery pressure.

Jiang R; Liu H; Pudasaini B; Zhang R; Xu JL; Wang L; Zhao QH; Yuan P; Guo
J; He J; Gong SG; Wu C; Wu WH; Luo CJ; Qiu HL; Jing ZC; Liu JM.

The clinical respiratory journal. 13(3):148-158, 2019 Mar. VI 1

BACKGROUND: Pulmonary hypertension patients with mean pulmonary artery
pressure (mPAP) >= 25 mm Hg had impaired cardiopulmonary exercise testing
(CPET). Borderline mean pulmonary pressures (boPAP; 21-24 mm Hg) represent
early pulmonary vasculopathy. The CPET characteristics of boPAP are a
matter of discussion. We aimed to determine the CPET profile of such
borderline hemodynamics.

METHODS: A matched case-control study was conducted on consecutive boPAP
patients at the Shanghai Pulmonary Hospital between Jan 2012 and Jan 2017.
Hemodynamics, echocardiography, the pulmonary function test (PFT) and CPET
parameters were compared between boPAP patients and normal mPAP patients
which were matched 1:1 by sex and age. Conditional logistic regression
analysis was performed to determine the efficacy of CPET in detecting

RESULTS: A total of 48 patients underwent RHC and CPET (24 Normal, 24
boPAP). There were no differences in the demographics, echocardiography
and PFT. BoPAP patients had significantly decreased VO2 at the anaerobic
threshold and peak VO2 /kg (858.4 +/- 246.5 mL/min vs 727.9 +/- 228.0
mL/min, P = 0.037; 21.1 +/- 6.4 mL/min/kg vs. 15.5 +/- 5.6 mL/min/kg, P =
0.001, respectively). Significant differences were not observed in
ventilation efficiency. A trend of impaired oxygen pulse and submaximal
exercise tolerance were observed in boPAP patients. Conditional logistical
regression analysis revealed the risk of boPAP increased by 2.493 (95%
confident interval: 1.388 to 4.476, P = 0.002) with every 5 mL/min/kg
decrease in peak VO2 /kg.

CONCLUSIONS: Patients with boPAP have a greater prevalence of exercise
intolerance, a trend of impaired oxygen pulse and submaximal exercise

Cardiopulmonary Function in Patients with Congenital Scoliosis: An Observational Study.

Lin Y, Shen J, Chen L, Yuan W, Cong H, Luo J, Kwan KYH

J Bone Joint Surg Am. 2019 Jun 19;101(12):1109-1118.

BACKGROUND: Patients with congenital scoliosis often have restrictive pulmonary
dysfunction on static pulmonary function testing (PFT). Although frequently
asymptomatic during daily activities, these patients are generally assumed to
have reduced exercise capacity. The aim of this study was to use dynamic
cardiopulmonary exercise testing (CPET) to investigate exercise capacity and its
association with spinal deformity in patients with congenital scoliosis.
METHODS: Sixty patients with congenital scoliosis who underwent preoperative
spinal radiography, PFT, and CPET were included from January 2014 to November
2017. The impact of thoracic spinal deformity and rib anomalies on pulmonary
function and physical capacity was investigated.
RESULTS: A significant deterioration in pulmonary function with increases in the
severity of the major thoracic curve was demonstrated by the forced expiratory
volume in 1 second (FEV1), forced vital capacity (FVC), and total lung capacity
(all p < 0.001). The ratio of FEV1 to FVC was similar regardless of thoracic
curve severity. A smaller tidal volume during exercise testing reflected
restrictive dysfunction in the patients with the most severe curves. CPET also
revealed a significant trend of faster breathing by patients with a severe
thoracic curve (p < 0.001). Exercise capacity indicators such as work rate (p =
0.019), heart rate (p = 0.015), and oxygen saturation (p = 0.006) were
significantly reduced only in patients with a thoracic curve of >100°. Pulmonary
dysfunction was the major contributor to exercise intolerance. Compared with mild
pulmonary dysfunction, moderate and severe dysfunction was associated with an
abnormal breathing pattern and lower work rate (p = 0.032) and peak oxygen intake
(p = 0.042), indicating worse exercise tolerance.
CONCLUSIONS: Congenital scoliosis leads to restrictive pulmonary dysfunction,
which reduces the tidal volume and forces patients to accelerate respiratory
rates during exercise. Patients with a thoracic curve of >100° are unable to
compensate and have significantly reduced exercise capacity.

Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome

Katarina Lien , Bjørn Johansen, Marit B. Veierød, Annicke S. Haslestad, Siv K. Bøhn,
Morten N. Melsom, Kristin R. Kardel & Per O. Iversen

Physiol Rep, 7 (11), 2019, e14138,

Post-exertional malaise and delayed recovery are hallmark symptoms of myalgic
encephalomyelitis/chronic fatigue syndrome (ME/CFS). Studies on
repeated cardiopulmonary exercise testing (CPET) show that previous exercise
negatively affects oxygen uptake (VO2) and power output (PO) in ME/CFS.
Whether this affects arterial lactate concentrations ([Laa]) is unknown. We
studied 18 female patients (18–50 years) fulfilling the Canadian Consensus
Criteria for ME/CFS and 15 healthy females (18–50 years) who underwent
repeated CPETs 24 h apart (CPET1 and CPET2) with [Laa] measured every
30th second. VO2 at peak exercise (VO2peak) was lower in patients than in
controls on CPET1 (P < 0.001) and decreased in patients on CPET2
(P < 0.001). However, the difference in VO2peak between CPETs did not differ
significantly between groups. [Laa] per PO was higher in patients during both
CPETs (Pinteraction < 0.001), but increased in patients and decreased in controls
from CPET1 to CPET2 (Pinteraction < 0.001). Patients had lower VO2
(P = 0.02) and PO (P = 0.002) at the gas exchange threshold (GET, the point
where CO2 production increases relative to VO2), but relative intensity
(%VO2peak) and [Laa] at GET did not differ significantly from controls on
CPET1. Patients had a reduction in VO2 (P = 0.02) and PO (P = 0.01) at
GET on CPET2, but no significant differences in %VO2peak and [Laa] at
GET between CPETs. Controls had no significant differences in VO2, PO or
%VO2peak at GET between CPETs, but [Laa] at GET was reduced on CPET2
(P = 0.008). In conclusion, previous exercise deteriorates physical performance
and increases [Laa] during exercise in patients with ME/CFS while it lowers
[Laa] in healthy subjects.

Improvement of cardiopulmonary function after minimally invasive surgical repair of pectus excavatum (Nuss procedure) in children.

Das BB; Recto MR; Yeh T;

Annals Of Pediatric Cardiology [Ann Pediatr Cardiol] 2019 May-Aug; Vol. 12 (2), pp. 77-82.

Background: Severe pectus excavatum in children may result in cardiorespiratory functional impairment; therefore, we evaluated cardiopulmonary response to exercise before and after the Nuss procedure.
Methods: Twenty-four physically active pediatric patients aged 9-18 years with severe pectus excavatum (Haller index >3.25) were included in the study. Cardiopulmonary exercise testing using treadmill and modified Bruce protocol was performed before and after the Nuss procedure.
Results: Maximal oxygen uptake and oxygen pulse improved by 40.6% (32 ± 13-45 ± 10 ml/kg/min; P = 0.0001) and 44.4% (9 ± 4-13 ± 5 ml/beat; P = 0.03), respectively, after surgical correction of pectus excavatum by Nuss procedure. Significant improvement in maximum voluntary ventilation and minute ventilation after Nuss procedure was also noted.
Conclusions: We found that, after repair of pectus excavatum by Nuss procedure, the exercise capacity as measured by maximal oxygen consumption improved significantly primarily due to increase in oxygen pulse, an indirect measurement of stroke volume.

Does exercise prescription based on estimated heart rate training zones exceed the ventilatory anaerobic threshold in patients with coronary heart disease undergoing usual-care cardiovascular rehabilitation? A United Kingdom perspective.

Pymer S; Nichols S; Birkett S; Carroll S; Ingle L;

European Journal Of Preventive Cardiology [Eur J Prev Cardiol] 2019 May 22, pp. 2047487319852711. Date of Electronic Publication: 2019 May 22.

Background: In the United Kingdom (UK), exercise intensity is prescribed from a fixed percentage range (% heart rate reserve (%HRR)) in cardiac rehabilitation programmes. We aimed to determine the accuracy of this approach by comparing it with an objective, threshold-based approach incorporating the accurate determination of ventilatory anaerobic threshold (VAT). We also aimed to investigate the role of baseline cardiorespiratory fitness status and exercise testing mode dependency (cycle vs. treadmill ergometer) on these relationships.
Design and Methods: A maximal cardiopulmonary exercise test was conducted on a cycle ergometer or a treadmill before and following usual-care circuit training from two separate cardiac rehabilitation programmes from a single region in the UK. The heart rate corresponding to VAT was compared with current heart rate-based exercise prescription guidelines.
Results: We included 112 referred patients (61 years (59-63); body mass index 29 kg·m-2 (29-30); 88% male). There was a significant but relatively weak correlation ( r = 0.32; p = 0.001) between measured and predicted %HRR, and values were significantly different from each other ( p = 0.005). Within this cohort, we found that 55% of patients had their VAT identified outside of the 40-70% predicted HRR exercise training zone. In the majority of participants (45%), the VAT occurred at an exercise intensity <40% HRR. Moreover, 57% of patients with low levels of cardiorespiratory fitness achieved VAT at <40% HRR, whereas 30% of patients with higher fitness achieved their VAT at >70% HRR. VAT was significantly higher on the treadmill than the cycle ergometer ( p < 0.001).
Conclusion: In the UK, current guidelines for prescribing exercise intensity are based on a fixed percentage range. Our findings indicate that this approach may be inaccurate in a large proportion of patients undertaking cardiac rehabilitation.


High-intensity interval training in cardiac resynchronization therapy: a randomized control trial.

Santa-Clara H; Abreu A; Melo X; Santos V; Cunha P; Oliveira M; Pinto R; Carmo MM;

European Journal Of Applied Physiology [Eur J Appl Physiol] 2019 May 23. Date of Electronic Publication: 2019 May 23.

Aims: To determine the effects of high-intensity interval training (HIIT) following cardiac resynchronization therapy (CRT) implantation in patients with chronic heart failure (CHF), on noninvasive estimates of systolic ventricular function, exercise performance, severity of symptoms and quality of life.
Methods: Cardiopulmonary exercise testing, resting transthoracic echocardiogram and health-related quality of life assessment were obtained before and at 6 months after CRT implantation in 37 patients with moderate-to-severe CHF. Patients were randomized after CRT to either a 24-week HIIT group (90-95% peak heart rate, 2 days per week) or to a usual care group (CON). Mixed design 2 × 2 repeated measures ANOVA were used to test for differences within and in-between groups.
Results: Improvements in health-related quality of life (HIIT = 98.54%, CON = 123.47%), NYHA class (HIIT = 43.44%, CON = 38.30%) HR recovery at minute 1 (HIIT = 32.32%, CON = 42.94%), pulse pressure at peak effort (HIIT = 14.06%, CON = 9.52%, LVEF (HIIT = 42.17%, CON = 51.10%) and LV Mass (HIIT = 13.26%, CON = 11.88%) were similar in both groups (p > 0.05). Significant increases in CPET duration in the HIIT group (25.94%), and increases in peak VO2 (HIIT = 8.64%, CON = 4.85%) and percent-predicted VO2 (HIIT = 10.57%, CON = 4.26%) in both groups, were observed in the intention-to-treat analysis.
Conclusion: Six months of HIIT in patients in CRT did not further improved indices of functional capacity and health-related quality of life, and LV structure and function, compared to CRT alone. However, HIIT led to further improvements in exercise performance. It remains unclear whether HIIT benefits patients in CRT to a similar degree as more conventional forms of exercise training previously shown to maximize benefits in CRT.

Characteristics and Safety of Cardiopulmonary Exercise Testing in Elderly Patients with Cardiovascular Diseases in Korea.

Kim BJ; Kim Y; Oh J; Jang J; Kang SM;

Yonsei Medical Journal [Yonsei Med J] 2019 Jun; Vol. 60 (6), pp. 547-553.

Purpose: Clinical use of cardiopulmonary exercise tests (CPETs) is increasing in elderly patients with cardiovascular (CV) diseases. However, data on Korean populations are limited. In this study, we aimed to examine the characteristics and safety of CPET in an elderly Korean population with CV disease.
Materials and Methods: We retrospectively analyzed records of 1485 patients (older than 65 years in age, with various underlying CV diseases) who underwent CPET. All CPET was performed using the modified Bruce ramp protocol.
Results: The mean age of patients was 71.6±4.7 years with 63.9% being men, 567 patients aged 60-65 years, 818 patients aged 70-79 years, and 100 patients aged 80-89 years. The mean respiratory exchange ratio was 1.09±0.14. During CPET, three adverse cardiovascular events occurred (total 0.20%), all ventricular tachycardia. All subjects showed an average exercise capacity of 21.3±5.5 mL/kg/min at peak VO₂ and 6.1±1.6 metabolic equivalents of task, and men showed better exercise capacity than women on most CEPT parameters. A significant difference was seen in peak oxygen uptake according to age group (65-69 years, 22.9±5.8; 70-79 years, 20.7±5.1; 80-89 years, 17.0±4.5 mL/kg/min, p<0.001). The most common causes for CPET termination were dyspnea (64.8%) and leg pain (24.3%), with higher incidence of leg pain in octogenarians compared to other age groups (65-69 years, 22.4%; 70-79 years, 24.6%; 80-89 years, 32.0%, p<0.001).
Conclusion: CPET was relatively a safe and useful modality to assess exercise capacity, even in an elderly Korean population with underlying CV diseases.

Persistent Long-Term Structural, Functional, and Metabolic Changes After Stress-Induced (Takotsubo) Cardiomyopathy.

Scally C, Rudd A, Mezincescu A, Wilson H, Srivanasan J, Horgan
G, Broadhurst P, Newby DE, Henning A, Dawson DK

Circulation. 2018 Mar 6;137(10):1039-1048

BACKGROUND: Takotsubo cardiomyopathy is an increasingly recognized acute heart
failure syndrome precipitated by intense emotional stress. Although there is an
apparent rapid and spontaneous recovery of left ventricular ejection fraction,
the long-term clinical and functional consequences of takotsubo cardiomyopathy
are ill-defined.
METHODS: In an observational case-control study, we recruited 37 patients with
prior (>12-month) takotsubo cardiomyopathy, and 37 age-, sex-, and
comorbidity-matched control subjects. Patients completed the Minnesota Living
with Heart Failure Questionnaire. All participants underwent detailed clinical
phenotypic characterization, including serum biomarker analysis, cardiopulmonary
exercise testing, echocardiography, and cardiac magnetic resonance including
cardiac 31P-spectroscopy.
RESULTS: Participants were predominantly middle-age (64±11 years) women (97%).
Although takotsubo cardiomyopathy occurred 20 (range 13-39) months before the
study, the majority (88%) of patients had persisting symptoms compatible with
heart failure (median of 13 [range 0-76] in the Minnesota Living with Heart
Failure Questionnaire) and cardiac limitation on exercise testing (reduced peak
oxygen consumption, 24±1.3 versus 31±1.3 mL/kg/min, P<0.001; increased VE/Vco2
slope, 31±1 versus 26±1, P=0.002). Despite normal left ventricular ejection
fraction and serum biomarkers, patients with prior takotsubo cardiomyopathy had
impaired cardiac deformation indices (reduced apical circumferential strain,
-16±1.0 versus -23±1.5%, P<0.001; global longitudinal strain, -17±1 versus
-20±1%, P=0.006), increased native T1 mapping values (1264±10 versus 1184±10 ms,
P<0.001), and impaired cardiac energetic status (phosphocreatine/γ-adenosine
triphosphate ratio, 1.3±0.1 versus 1.9±0.1, P<0.001).
CONCLUSIONS: In contrast to previous perceptions, takotsubo cardiomyopathy has
long-lasting clinical consequences, including demonstrable symptomatic and
functional impairment associated with persistent subclinical cardiac dysfunction.
Taken together our findings demonstrate that after takotsubo cardiomyopathy,
patients develop a persistent, long-term heart failure phenotype.

Relation of Fontan Baffle Stroke Volume to Fontan Failure and Lower Exercise Capacity in Patients With an Atriopulmonary Fontan.

Alsaied T; van der Ven JPG; Juggan S; Sleeper LA; Azcue N; Kroft LJ; Powell AJ; Helbing WA; Rathod RH;

The American Journal Of Cardiology [Am J Cardiol] 2019 Apr 09. Date of Electronic Publication: 2019 Apr 09.

Fontan failure remains a significant problem, especially in patients with an atriopulmonary Fontan. Fontan baffle volume change during the cardiac cycle (Fontan baffle stroke volume) may affect outcomes in Fontan circulation. Assuming that increased Fontan baffle stroke volume is associated with increased energy loss in the baffle, we hypothesized that higher baffle stroke volume is associated with worse exercise capacity and increased incidence of Fontan failure. Patients from 6 centers with an atriopulmonary or lateral tunnel Fontan operation were included if they had a cardiac magnetic resonance (CMR) study and an adequate cardiopulmonary exercise test. Fontan baffle stroke volume was defined as the difference between maximum and minimum Fontan baffle volumes. Fontan failure was defined as death, listing for transplantation, heart failure symptoms requiring medications, or peak VO2 below 16 ml/kg/min. The study group consisted of 107 patients (median age 19 years, interquartile range, 14 to 29 years). Most patients (84%) had lateral tunnel procedure. During a median follow-up period of 6.8 [interquartile range: 3.2 to 8.8] years after the CMR, 25 (23%) patients had Fontan failure (7 deaths, 3 listed for transplantation, and 15 with heart failure symptoms). Predictors of Fontan failure on multivariable analysis were ventricular tachycardia, protein losing enteropathy, and additionally in atriopulmonary Fontan only, larger Fontan baffle stroke volume. Predictors of lower peak VO2 on multivariable analysis were older age at CMR and additionally in atriopulmonary Fontan only, larger Fontan baffle stroke volume. In conclusion, larger Fontan baffle stroke volume was independently associated with lower peak VO2 and Fontan failure in atriopulmonary Fontan.


Chronotropic incompetence and myocardial injury after noncardiac surgery: planned secondary analysis of a prospective observational international cohort study.

Abbott TEF; Pearse RM; Beattie WS; Phull M; Beilstein C; Raj A; Grocott MPW; Cuthbertson BH; Wijeysundera D; Ackland GL;

British Journal Of Anaesthesia [Br J Anaesth] 2019 Apr 24. Date of Electronic Publication: 2019 Apr 24.

Background: Physiological measures of heart failure are common in surgical patients, despite the absence of a diagnosis. Heart rate (HR) increases during exercise are frequently blunted in heart failure (termed chronotropic incompetence), which primarily reflects beta-adrenoreceptor dysfunction. We examined whether chronotropic incompetence was associated with myocardial injury after noncardiac surgery.
Methods: This was a predefined analysis of an international cohort study where participants aged ≥40 yr underwent symptom-limited cardiopulmonary exercise testing before noncardiac surgery. Chronotropic incompetence was defined as the ratio of increase in HR during exercise to age-predicted maximal increase in HR <0.6. The primary outcome was myocardial injury within 3 days after surgery, defined by high-sensitivity troponin assays >99th centile. Explanatory variables were biomarkers for heart failure (ventilatory efficiency slope [minute ventilation/carbon dioxide production] ≥34; peak oxygen consumption ≤14 ml kg-1 min-1; HR recovery ≤6 beats min-1 decrease 1 min post-exercise; preoperative N-terminal pro-B-type natriuretic peptide [NT pro-BNP] >300 pg ml-1). Myocardial injury was compared in the presence or absence of sympathetic (i.e. chronotropic incompetence) or parasympathetic (i.e. impaired HR recovery after exercise) thresholds indicative of dysfunction. Data are presented as odds ratios (ORs) (95% confidence intervals).
Results: Chronotropic incompetence occurred in 396/1325 (29.9%) participants; only 16/1325 (1.2%) had a heart failure diagnosis. Myocardial injury was sustained by 162/1325 (12.2%) patients. Raised preoperative NT pro-BNP was more common when chronotropic incompetence was <0.6 (OR: 1.57 [1.11-2.23]; P=0.011). Chronotropic incompetence was not significantly associated with myocardial injury (OR: 1.05 [0.74-1.50]; P=0.78), independent of rate-limiting therapy. HR recovery <12 beats min-1 decrease after exercise was associated with myocardial injury in the presence (OR: 1.62 [1.05-2.51]; P=0.03) or absence (OR: 1.60 [1.06-2.39]; P=0.02) of chronotropic incompetence.
Conclusions: Chronotropic incompetence is common in surgical patients. In contrast to parasympathetic dysfunction which was associated with myocardial injury, preoperative chronotropic incompetence (suggestive of sympathetic dysfunction) was not associated with postoperative myocardial injury.