Category Archives: Publications

Operative and Functional Outcome After Pulmonary Endarterectomy for Advanced Thromboembolic Pulmonary Hypertension

Leung Wai Sang,
Stephane; Morin, Jean‐Francois; Hirsch, Andrew.

Journal of Cardiac
Surgery, January 2016, Vol. 31 Issue: Number 1 p3-8, 6p;


To  evaluate the midterm hemodynamic and functional outcome of pulmonary
endarterectomy (PEA) for patients with advanced chronic thromboembolic
pulmonary hypertension (CTEPH). Thirty‐eight consecutive patients
underwent PEA for CTEPH from May 2004 to March 2012. All patients were
followed prospectively at six months postoperatively and annually
thereafter. Each patient underwent serial cardiopulmonary exercise
testing (CPET) and transthoracic echocardiography, and were followed
for up to four years. Overall, 31.5% (12/38) of patients had Jamieson
class II disease while 65.8% (25/38) had class III disease. There were
three in‐hospital mortalities (7.9%), all of which had baseline
pulmonary vasculature resistance (PVR) greater than
1400 dynes‐sec‐cm−5. Preoperative PVR and mean pulmonary artery
pressure were 1209 ± 723 dynes‐sec‐cm−5and 50 ± 14 mmHg, respectively,
signifying a high‐risk operative group. Ninety‐seven percent of
patients were in NYHA class III or IV preoperatively. At median
follow‐up of 29 months 89.5% (17/19) of patients were in NYHA class I
or II. CPET revealed a progressive increase in peak oxygen consumption
from 16.5 ± 4.1 ml/kg/min at first follow‐up, to a plateau of
20.2 ± 5.6 ml/kg/min (p = 0.032) at two years. CPET can be used to
quantify progress in functional capacity post‐CTEPH, although
improvements in peak oxygen consumption plateau at two years.

Oxygen uptake is more efficient in idiopathic pulmonary arterial hypertension than in chronic thromboembolic pulmonary hypertension

Shi, Xiaofang; Guo, Jian; Gong, Sugang; Sapkota, Rikesh; Yang, Wenlan;
Liu, Hui; Xiang, Wenjing; Wang, Lan; Sun, Xingguo; Liu, Jinming.

Respirology, January 2016, Vol. 21 Issue: Number 1 p149-156, 8p;
Abstract: The responses of oxygen uptake efficiency (OUE) during
cardiopulmonary exercise training (CPET) have not been reported in
patients with pulmonary hypertension. We aimed to investigate the
differences in OUE between patients with idiopathic pulmonary arterial
hypertension (IPAH) and chronic thromboembolic pulmonary hypertension
(CTEPH). Forty‐four patients with IPAHand 29 patients with CTEPH were
retrospectively enrolled into our study. All patients underwent
right‐heart catheterization, pulmonary function test and performed the
6‐min walk test and CPET. We found that oxygen uptake efficiency
plateau (OUEP) and oxygen uptake efficiency at anaerobic threshold
(OUE@AT) was significantly higher in IPAH than that in CTEPH (both
P= 0.002). However, patients with CTEPH had lower mean pulmonary artery
pressure, pulmonary vascular resistance and transpulmonary gradient
(all P< 0.05). The correlation between OUEP and heart rate at anaerobic
threshold (HR_AT) was significant (r = 0.376, P< 0.05); however, no
statistically significant correlation was found with ventilation at
anaerobic threshold (VE_AT) (r = −0.074, P> 0.05) in patients with
IPAH. In patients with CTEPH, both anaerobic threshold (r = 0.307,
P> 0.05) and VE_AT (r = −0.709, P< 0.0001) were reduced. OUEP were
higher in WHO functional class I/IIpatients than in WHO functional class
III/IVpatients (all P< 0.05). OUEP and OUE@ATare higher in IPAHthan that
in CTEPH not in proportion to haemodynamics, probably due to differences
in cardiac function and pulmonary vascular occlusion. OUEP correlates
well with the exercise capacity and the severity of the disease.
Responses of oxygen uptake efficiency during cardiopulmonary exercise
testing in patients with pulmonary hypertension are reported. We
observed a higher oxygen uptake efficiency in patients with idiopathic
pulmonary arterial hypertension compared to patients with chronic
thromboembolic pulmonary hypertension. The oxygen uptake efficiency
plateau correlates with exercise capacity and disease severity.

Cardiopulmonary Exercise Testing in Patients with Asymptomatic or Equivocal Symptomatic Aortic Stenosis: Feasibility, Reproducibility, Safety and Information Obtained on Exercise Physiology

van Le,
Douet; Jensen, Gunnar Vagn Hagemann; Carstensen, Steen; Kjøller-Hansen,

Cardiology, November 2015, Vol. 133 Issue: Number 3 p147-156,

Objective:The aim of this study was to determine the
feasibility, reproducibility, safety and information obtained on
exercise physiology from cardiopulmonary exercise testing (CPX) in
patients with aortic stenosis.
Methods:Patients with an aortic valve
area (AVA) <1.3 cm2who were judged asymptomatic or equivocal
symptomatic underwent CPX and an inert gas rebreathing test. Only those
where comprehensive evaluation of CPX results indicated haemodynamic
compromise from aortic stenosis were referred for valve replacement.
Results:The mean patient age was 72 (±9) years; an AVA index <0.6
cm2/m2and equivocal symptomatic status were found in 90 and 70%,
respectively. CPX was feasible in 130 of the 131 patients. The
coefficients of repeatability by test-retest were 5.4% (pVO2) and 4.6%
(peak O2pulse). A pVO2<83% of the expected was predicted by a lower
stroke volume at exercise, lower peak heart rate and FEV1, and higher
VE/VCO2, but not by AVA index. Equivocal symptomatic status and a low
gradient but high valvulo-arterial impedance were associated with a
lower pVO2, but not with an inability to increase stroke volume. In
total, 18 patients were referred for valve replacement. At 1 year, no
cardiovascular deaths had occurred.
Conclusions:CPX was feasible and
reproducible and provided comprehensive data on exercise physiology. A
CPX-guided treatment strategy was safe up to 1 year.

Cardiopulmonary exercise testing versus spirometry as predictors of cardiopulmonary complications after colorectal surgery

Nikolopoulos,  I.; Ellwood, M.; George, M.; Carapeti, E.; Williams, A..

European Surgery (Acta Chirurgica Austriaca), December 2015, Vol. 47 Issue:
Number 6 p324-330, 7p;

Abstract: To determine the predictive value of
spirometry and cardiopulmonary exercise testing (CPET) preoperatively
in patients scheduled to undergo elective colorectal surgery. We
compared the preoperative results with the incidence of postoperative
cardiopulmonary complications.  A total of 103   patients were scheduled
to undergo preoperative CPET and spirometry; 14
patients did not attend their appointments and another 20 were unable
to perform the test. In all, 69 patients (median age 60 years (range
25–85), 35 males) successfully completed cycle ergometry and lung
function tests. Forced expiratory volume in 1 s (FEV1), percent forced
expiratory volume in 1 s (FEV1/forced vital capacity (FVC)) and
anaerobic threshold (AT) were measured. Patients were divided
postoperatively according to whether cardiopulmonary complications were
absent (group A) or present (group B).  Postoperative
cardiopulmonary complications developed in 8 of the 69 patients (12 %).
Thirty day mortality was 3 %. AT was significantly higher in group A
(mean AT = 13.8; SD ± 3.0; range = 8.1–20.8) than in group B
(mean = 10.91; SD ± 3.0; Range = 7.9–12), (p= 0.0006). Spirometric
pulmonary function tests (FEV1, p= 0.09) and (FEV1/FVC, p= 0.08) showed
no intergroup differences. The median hospital length of stay (HLOS)
was significantly higher in the group of patients that suffered
cardiopulmonary complications (p= 0.0282).     CPET
allows the prediction of postoperative cardiopulmonary complications
which cannot be anticipated by spirometry. Early detection of high risk
patients facilitates the planning of patient specific management
strategies which are likely to improve outcome through invasive
monitoring and optimisation of cardio-respiratory function.

Usefulness of C-Reactive Protein Plasma Levels to Predict Exercise Intolerance in Patients With Chronic Systolic Heart Failure

Justin McNair; Fronk, Daniel Taylor; Cei, Laura Freeman; Carbone,
Salvatore; Erdle, Claudia Oddi; Abouzaki, Nayef Antar; Melchior, Ryan
David; Thomas, Christopher Scott; Christopher, Sanah; Turlington,
Jeremy Shane; Trankle, Cory Ross; Thurber, Clinton Joseph; Evans,
Ronald Kenneth; Dixon, Dave L.; Van Tassell, Benjamin Wallace; Arena,
Ross; Abbate, Antonio.

The American Journal of Cardiology, January
2016, Vol. 117 Issue: Number 1 p116-120, 5p;

Abstract: Patients with
heart failure (HF) have evidence of chronic systemic inflammation.
Whether inflammation contributes to the exercise intolerance in
patients with HF is, however, not well established. We hypothesized
that the levels of C-reactive protein (CRP), an established
inflammatory biomarker, predict impaired cardiopulmonary exercise
performance, in patients with chronic systolic HF. We measured CRP
using high-sensitivity particle-enhanced immunonephelometry in 16
patients with ischemic heart disease (previous myocardial infarction)
and chronic systolic HF, defined as a left ventricular ejection
fraction ≤50% and New York Heart Association class II-III symptoms. All
subjects with CRP >2 mg/L, reflecting systemic inflammation, underwent
cardiopulmonary exercise testing using a symptom-limited ramp protocol.
CRP levels predicted shorter exercise times (R = −0.65, p = 0.006),
lower oxygen consumption (VO2) at the anaerobic threshold (R = −0.66,
p = 0.005), and lower peak VO2(R = −0.70, p = 0.002), reflecting worse
cardiovascular performance. CRP levels also significantly correlated
with an elevated ventilation/carbon dioxide production slope
(R = +0.64, p = 0.008), a reduced oxygen uptake efficiency slope
(R = −0.55, p = 0.026), and reduced end-tidal CO2level at rest and with
exercise (R = −0.759, p = 0.001 and R = −0.739, p = 0.001,
respectively), reflecting impaired gas exchange. In conclusion, the
intensity of systemic inflammation, measured as CRP plasma levels, is
associated with cardiopulmonary exercise performance, in patients with
ischemic heart disease and chronic systolic HF. These data provide the
rationale for targeted anti-inflammatory treatments in HF.

Rationale and Design of a Randomized Controlled Trial Evaluating Whole Muscle Exercise Training Effects in Outpatients with Pulmonary Arterial Hypertension

Sanchis-Gomar, Fabian;  González-Saiz, Laura; Sanz-Ayan, Paz; Fiuza-Luces, Carmen;
Quezada-Loaiza, Carlos; Flox-Camacho, Angela; Santalla, Alfredo;
Munguía-Izquierdo, Diego; Santos-Lozano, Alejandro; Pareja-Galeano,
Helios; Ara, Ignacio; Escribano-Subías, Pilar; Lucia, Alejandro.
Cardiovascular Drugs and Therapy, December 2015, Vol. 29 Issue: Number
6 p543-550, 8p;

Abstract: Physical exercise is an important component
in the management of pulmonary artery hypertension (PAH). The aim of
this randomized controlled trial (RCT) is to determine the effects of
an 8-week intervention combining muscle resistance, aerobic and
inspiratory pressure load exercises in PAH outpatients.
The RCT will be conducted from September 2015 to September 2016
following the recommendations of the Consolidated Standards of Reported
Trials (CONSORT), with a total sample size of n ≥ 48 (≥24
participants/group). We will determine the effects of the intervention
on: (i) skeletal-muscle power and mass (primary end points); and (ii)
NT-proBNP, cardiopulmonary exercise testing variables (VO2peak,
ventilatory equivalent for CO2at the anaerobic threshold (VE/VCO2at the
AT), end-tidal pressure of CO2at the anaerobic threshold (PETCO2at the
AT), 6-min walking distance (6MWD), maximal inspiratory pressure
(PImax), health-related quality of life (HRQoL), objectively-assessed
spontaneous levels of physical activity, and safety (secondary end
points).                   This trial will provide insight into
biological mechanisms of the disease and indicate the potential
benefits of exercise in PAH outpatients, particularly on muscle power.

Protocol for exercise hemodynamic assessment: performing an invasive cardiopulmonary exercise test in clinical practice

Berry, Natalia
C.; Manyoo, Agarwal; Oldham, William M.; Stephens, Thomas E.;
Goldstein, Ronald H.; Waxman, Aaron B.; Tracy, Julie A.; Leary, Peter
J.; Leopold, Jane A.; Kinlay, Scott; Opotowsky, Alexander R.; Systrom,
David M.; Maron, Bradley A..

Pulmonary Circulation (JSTOR), December 2015, Vol. 5 Issue: Number 4 p610-618, 9p;

Abstract: Invasive cardiopulmonary exercise testing (iCPET) combines full central
hemodynamic assessment with continuous measurements of pulmonary gas
exchange and ventilation to help in understanding the pathophysiology
underpinning unexplained exertional intolerance. There is increasing
evidence to support the use of iCPET as a key methodology for
diagnosing heart failure with preserved ejection fraction and
exercise-induced pulmonary hypertension as occult causes of exercise
limitation, but there is little information available outlining the
methodology to use this diagnostic test in clinical practice. To bridge
this knowledge gap, the operational protocol for iCPET at our
institution is discussed in detail. In turn, a standardized iCPET
protocol may provide a common framework to describe the evolving
understanding of mechanism(s) that limit exercise capacity and to
facilitate research efforts to define novel treatments in these

Comparative effectiveness of sildenafil for pulmonary hypertension due to left heart disease with HFrEF

Jiang, Rong; Wang, Lan; Zhu,
Chang-Tai; Yuan, Ping; Pudasaini, Bigyan; Zhao, Qin-Hua; Gong, Su-Gang;
He, Jing; Liu, Jin-Ming; Hu, Qing-Hua.

Hypertension Research, December 2015, Vol. 38 Issue: Number 12 p829-839, 11p;


There is no cure for pulmonary hypertension due to left heart disease (PH-LHD), but
the rationale for using sildenafil to treat pulmonary arterial
hypertension with heart failure with reduced ejection fraction (HFrEF)
has been supported by short-term studies. We performed a meta-analysis
to evaluate the effectiveness of sildenafil for PH-LHD with HFrEF. A
systematic literature search of PubMed, EMBASE and the Cochrane Central
Register of Controlled Trials was conducted from inception through
October 2014 for randomized trials and for observational studies with
control groups, evaluating the effectiveness of sildenafil to treat
PH-LHD with HFrEF. Sildenafil therapy decreased pulmonary arterial
systolic pressure both at the acute phase and at the 6-month follow-up
(weighted mean difference (WMD): −6.03 mm Hg, P=0.02; WMD:
−11.47 mm Hg, P<0.00001, respectively). Sildenafil was found to reduce
mean pulmonary artery pressure (WMD: −3 mm Hg, P=0.0004) and pulmonary
vascular resistance (WMD: −60.0 dynes cm−5, P=0.01) at the 3-month
follow-up. Oxygen consumption at peak significantly increased to
3.66 ml min−1kg−1(P<0.00001), 3.36 ml min−1kg−1(P<0.00001) and
2.60 ml min−1kg−1(P=0.03) at 3, 6 and 12 months, respectively. There
were significant reductions in ventilation to CO2production slope of
−2.00, −4.68 and −7.12 at 3, 6 and 12 months, respectively (P<0.00001).
Sildenafil was superior to placebo regarding left ventricular ejection
fraction at the 6-month follow-up (WMD: 4.35, P<0.00001), and it
significantly improved quality of life. Sildenafil therapy could
effectively improve pulmonary hemodynamics and cardiopulmonary exercise
testing measurements of PH-LHD with HFrEF, regardless of acute or
chronic treatment.

Exercise Performance in Children and Young Adults After Complete and Incomplete Repair of Congenital Heart Disease

Rosenblum, Omer; Katz,
Uriel; Reuveny, Ronen; Williams, Craig; Dubnov-Raz, Gal.

Pediatric Cardiology, December 2015, Vol. 36 Issue: Number 8 p1573-1581, 9p;

Abstract: Few previous studies have addressed exercise capacity in
patients with corrected congenital heart disease (CHD) and significant
anatomical residua. The aim of this study was to determine the aerobic
fitness and peak cardiac function of patients with corrected CHD with
complete or incomplete repairs, as determined by resting
echocardiography. Children, adolescents and young adults (<40 years)
with CHD from both sexes, who had previously undergone biventricular
corrective therapeutic interventions (n= 73), and non-CHD control
participants (n= 76) underwent cardiopulmonary exercise testing. The
CHD group was further divided according to the absence/presence of
significant anatomical residua on a resting echocardiogram
(“complete”/“incomplete” repair groups). Aerobic fitness and cardiac
function were compared between groups using linear regression and
analysis of covariance. Peak oxygen consumption, O2pulse and
ventilatory threshold were significantly lower in CHD patients compared
with controls (all p< 0.01). Compared with the complete repair group,
the incomplete repair group had a significantly lower mean peak work
rate, age-adjusted O2pulse (expressed as % predicted) and a higher
VE/VCO2ratio (all p≤ 0.05). Peak oxygen consumption was comparable
between the subgroups. Patients after corrected CHD have lower peak and
submaximal exercise parameters. Patients with incomplete repair of
their heart defect had decreased aerobic fitness, with evidence of
impaired peak cardiac function and lower pulmonary perfusion. Patients
that had undergone a complete repair had decreased aerobic fitness
attributed only to deconditioning. These newly identified differences
explain why in previous studies, the lowest fitness was seen in
patients with the most hemodynamically significant heart