Category Archives: Publications

Exertional dyspnoea in interstitial lung diseases: the clinical utility of cardiopulmonary exercise testing.

Eur Respir Rev. 2017 Feb 21;26(143).

Bonini M, Fiorenzano G.

Interstitial lung diseases (ILDs) represent a heterogeneous group of pathologies
characterised by alveolar and interstitial damage, pulmonary inflammation
(usually associated with fibrosis), decreased lung function and impaired gas
exchange, which can be attributed to either a known or an unknown aetiology.
Dyspnoea is one of the most common and disabling symptoms in patients with ILD,
significantly impacting quality of life. The mechanisms causing dyspnoea are
complex and not yet fully understood. However, it is recognised that dyspnoea
occurs when there is an imbalance between the central respiratory efferent drive
and the response of the respiratory musculature. The respiratory derangement
observed in ILD patients at rest is even more evident during exercise.
Pathophysiological mechanisms responsible for exertional dyspnoea and reduced
exercise tolerance include altered respiratory mechanics, impaired gas exchange,
cardiovascular abnormalities and peripheral muscle dysfunction.This review
describes the respiratory physiology of ILD, both at rest and during exercise,
and aims to provide comprehensive and updated evidence on the clinical utility of
the cardiopulmonary exercise test in the assessment and management of these
pathological entities. In addition, the role of exercise training and pulmonary
rehabilitation programmes in the ILD population is addressed.

Cardiopulmonary exercise testing: A contemporary and versatile clinical tool.

Cleve Clin J Med. 2017 Feb;84(2):161-168.

Leclerc K.

Cardiopulmonary exercise testing (CPET) helps in detecting disorders of the
cardiovascular, pulmonary, and skeletal muscle systems. It has a class I
(indicated) recommendation from the American College of Cardiology and American
Heart Association for evaluating exertional dyspnea of uncertain cause and for
evaluating cardiac patients being considered for heart transplant. Advances in
hardware and software and ease of use have brought its application into the
clinical arena to the point that providers should become familiar with it and
consider it earlier in the evaluation of their patients.

Associations of cardiovascular and all-cause mortality events with oxygen uptake at ventilatory threshold.

Int J Cardiol. 2017 Feb 10. pii: S0167-5273(16)32158-1.

Kunutsor SK(1), Kurl S(2), Khan H(3), Zaccardi F(4), Laukkanen JA(5).

BACKGROUND: Oxygen uptake (VO2) at ventilatory threshold (VT), is a
cardiopulmonary exercise testing parameter which may be a proxy for peak VO2. We
aimed to assess the associations of VO2 at VT with sudden cardiac death (SCD),
fatal coronary heart disease (CHD) and cardiovascular disease (CVD), and
all-cause mortality.
METHODS AND RESULTS: VO2 at VT was assessed during a submaximal exercise test
using respiratory gas analyzers in the Kuopio Ischemic Heart Disease cohort of
1639 middle-aged men. Hazard ratios (HRs) (95% CIs) were assessed. During a
median follow-up of 25.6years, 121 SCDs, 202 fatal CHDs, 312 fatal CVDs, and 703
all-cause mortality events occurred. VO2 at VT was correlated with peak VO2
(r=0.90) and linearly associated with each outcome. Comparing extreme quartiles
of VO2 at VT, the HRs (95% CIs) for SCD, fatal CHD, fatal CVD, and all-cause
mortality on adjustment for established risk factors were 0.37 (0.18-0.78), 0.32
(0.18-0.57), 0.45 (0.30-0.69), and 0.50 (0.38-0.64) respectively. The HRs were
1.02 (0.36-2.91), 1.43 (0.63-3.25), 1.46 (0.79-2.71), and 1.02 (0.69-1.51)
respectively on further adjustment for peak VO2. Addition of VO2 at VT to a CVD
mortality risk prediction model containing established risk factors significantly
improved risk discrimination and reclassification at 25years.
CONCLUSIONS: There are linear and inverse associations of VO2 at VT with fatal
cardiovascular and all-cause mortality events, which are dependent on peak VO2.
Inclusion of VO2 at VT in the standard established risk factors panel
significantly improves the prediction and classification of long-term CVD
mortality risk.

Validation of preoperative cardiopulmonary exercise testing‐derived variables to predict in‐hospital morbidity after major colorectal surgery

West, M. A.; Asher, R.; Browning, M.; Minto, G.; Swart, M.;
Richardson, K.; McGarrity, L.; Jack, S.; Grocott, M. P. W.; Challand,
C.; wan Lai, C.; Struthers, R.; Sneyd, R.; Psarelli, E..

British Journal of Surgery: BJS, May 2016, Vol. 103 Issue: Number 6 p744-752,

Abstract: In single‐centre studies, postoperative complications are
associated with reduced fitness. This study explored the relationship
between cardiorespiratory fitness variables derived by cardiopulmonary
exercise testing (CPET) and in‐hospital morbidity after major elective
colorectal surgery. Patients underwent preoperative CPETwith recording
of in‐hospital morbidity. Receiver operating characteristic (ROC)
curves and logistic regression were used to assess the relationship
between CPET variables and postoperative morbidity. Seven hundred and
three patients from six centres in the UK were available for analysis
(428 men, 275 women). ROCcurve analysis of oxygen uptake at estimated
lactate threshold (V˙o2at θ^L) and at peak exercise (V˙o2peak) gave an
area under the ROCcurve (AUROC) of 0·79 (95 per cent c.i. 0·76 to 0·83;
P< 0·001; cut‐off 11·1 ml per kg per min) and 0·77 (0·72 to 0·82; P<
0·001; cut‐off 18·2 ml per kg per min) respectively, indicating that
they can identify patients at risk of postoperative morbidity. In a
multivariable logistic regression model, selected CPETvariables and
body mass index (BMI) were associated significantly with increased odds
of in‐hospital morbidity (V˙o2at θ^L11·1 ml per kg per min or less:
odds ratio (OR) 7·56, 95 per cent c.i. 4·44 to 12·86, P< 0·001;
V˙o2peak18·2 ml per kg per min or less: OR2·15, 1·01 to 4·57, P =0·047;
ventilatory equivalents for carbon dioxide at estimated lactate
threshold (V˙E/V˙co2at θ^L) more than 30·9: OR1·38, 1·00 to 1·89, P
=0·047); BMIexceeding 27 kg/m2: OR1·05, 1·03 to 1·08, P< 0·001). A
laparoscopic procedure was associated with a decreased odds of
complications (OR0·30, 0·02 to 0·44; P =0·033). This model was able to
discriminate between patients with, and without in‐hospital morbidity
(AUROC0·83, 95 per cent c.i. 0·79 to 0·87). No adverse clinical events
occurred during CPET across the six centres. These data provide further
evidence that variables derived from preoperative CPETcan be used to
assess risk before elective colorectal surgery. Validated risk
assessment; (AN 38537189)

2016 Focused Update: Clinical Recommendations for Cardiopulmonary Exercise Testing Data Assessment in Specific Patient Populations.

Circulation.133(24).,e694/711, 2016

Abstract: In the past several decades, cardiopulmonary exercise testing (CPX) has seen an exponential increase in its evidence base. The growing volume of evidence in support of CPX has precipitated the release of numerous scientific statements by societies and associations. In 2012, the European Association for Cardiovascular Prevention & Rehabilitation and the American Heart Association developed a joint document with the primary intent of redefining CPX analysis and reporting in a way that would streamline test interpretation and increase clinical application. Specifically, the 2012 joint scientific statement on CPX conceptualized an easy-to-use, clinically meaningful analysis based on evidence-vetted variables in color-coded algorithms; single-page algorithms were successfully developed for each proposed test indication. Because of an abundance of new CPX research in recent years and a reassessment of the current algorithms in light of the body of evidence, a focused update to the 2012 scientific statement is now warranted. The purposes of this update are to confirm algorithms included in the initial scientific statement not requiring revision, to propose revisions to algorithms included in the initial scientific statement, to propose new algorithms based on emerging scientific evidence, to further clarify the application of oxygen consumption at ventilatory threshold, to describe CPX variables with an emerging scientific evidence base, to describe the synergistic value of combining CPX with other assessments, to discuss personnel considerations for CPX laboratories, and to provide recommendations for future CPX research.

Right Ventricular Functional Reserve in Pulmonary Arterial Hypertension

Circulation.  133(24):2413-22, 2016 Jun 14.

Tedford,Ryan J. From Divisions of Cardiology (S.H., B.A.H., E.T., A.C.B.,
P.S.R., D.A.K., R.J.T.), Pulmonary and Critical Care (S.C.M., R.L.D.,
T.M.K., P.M.H.), and Rheumatology (L.K.H., A.A.S., Z.M., F.M.W.),
Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD;
and Departments of Radiology (C.P.C.-V., S.L.Z.) and Biomedical
Engineering (D.A.K.), Johns Hopkins Medical Institutions, Baltimore, MD.

BACKGROUND: Right ventricular (RV) functional reserve affects functional
capacity and prognosis in patients with pulmonary arterial hypertension
(PAH). PAH associated with systemic sclerosis (SSc-PAH) has a
substantially worse prognosis than idiopathic PAH (IPAH), even though many
measures of resting RV function and pulmonary vascular load are similar.
We therefore tested the hypothesis that RV functional reserve is depressed
in SSc-PAH patients.

CONCLUSIONS: RV contractile reserve is depressed in SSc-PAH versus IPAH
subjects, associated with reduced calcium recycling. During exercise, this
results in ventricular-pulmonary vascular uncoupling and acute RV
dilation. RV dilation during exercise can predict adverse
ventricular-vascular coupling in PAH patient

Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign

A Scientific Statement From the American Heart Association

Robert Ross, PhD, FAHA,
Steven N. Blair, PED, FAHA,
Ross Arena, PhD, PT, FAHA   et al.

Mounting evidence has firmly established that low levels
of cardiorespiratory fitness (CRF) are associated with a high risk of
cardiovascular disease, all-cause mortality, and mortality rates attributable
to various cancers. A growing body of epidemiological and clinical evidence
demonstrates not only that CRF is a potentially stronger predictor of
mortality than established risk factors such as smoking, hypertension,
high cholesterol, and type 2 diabetes mellitus, but that the addition of
CRF to traditional risk factors significantly improves the reclassification
of risk for adverse outcomes. The purpose of this statement is to review
current knowledge related to the association between CRF and health
outcomes, increase awareness of the added value of CRF to improve
risk prediction, and suggest future directions in research. Although the
statement is not intended to be a comprehensive review, critical references
that address important advances in the field are highlighted. The underlying
premise of this statement is that the addition of CRF for risk classification
presents health professionals with unique opportunities to improve patient
management and to encourage lifestyle-based strategies designed to
reduce cardiovascular risk. These opportunities must be realized to
optimize the prevention and treatment of cardiovascular disease and hence
meet the American Heart Association’s 2020 goals.

Abnormal heart-rate response during cardiopulmonary exercise testing identifies cardiac dysfunction in symptomatic patients with non-obstructive coronary artery disease

Sundeep Chaudhry , Naresh Kumar, Hushyar Behbahani , Akshay Bagai , Binoy K. Singh , NickMenasco , Gregory D. Lewis , Laurence Sperling , Jonathan Myers

International Journal of Cardiology 228 (2017) 114–121

Background: Symptomatic non-obstructive coronary artery disease is a growing clinical dilemma for whic hcontemporary testing is proving to be of limited clinical utility. New methods are needed to identify cardiac dysfunction.
Methods and results: This is a prospective observational cohort study conducted from December 2013 to August 2015 in two outpatient cardiology clinics (symptomatic cohort) and 24 outpatient practices throughout the US (healthy cohort) with centralized methodology and monitoring to compare heart-rate responses during cardiopulmonary exercise testing (CPET). Participants were 208 consecutive patients (median age, 61; range, 32–86 years) with exercise intolerance and without prior heart or lung disease in whom coronary anatomy was defined and 116 healthy subjects (median age, 45; range, 26–66 years). Compared to stress ECG, the novel change in heartrate as a function of work-rate parameter (ΔHR-WR Slope) demonstrated significantly higher sensitivity to detect under-treated atherosclerosis with similar specificity. In men, area under the ROC curve increased from 60% to 94% for non-obstructive CAD and from 64% to 80% for obstructive CAD. In women,  AUC increased from 64% to 85% for non-obstructive CAD and from 66% to 90% for obstructive CAD. ΔHR-WR Slope correctly reclassified abnormal studies in the non-obstructive CADgroup from 22% to 81%; in the obstructive CAD group from18% to 84% and in the revascularization group from 35% to 78%.
Conclusion: Abnormal heart-rate response during CPET is more effective than stress ECG for identifying undertreated atherosclerosis and may be of utility to identify cardiac dysfunction in symptomatic patients with normal routine cardiac testing.