Category Archives: Publications

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

A Systematic Review of Reference Values in Pediatric Cardiopulmonary Exercise Testing

Blais, Samuel; Berbari, Jade; Counil,
Francois-Pierre; Dallaire, Frederic.

Pediatric Cardiology, December
2015, Vol. 36 Issue: Number 8 p1553-1564, 12p;

Cardiopulmonary exercise testing (CPET) is used for the diagnosis and
prognosis of cardiovascular and pulmonary conditions in children and
adolescents. Several authors have published reference values for
pediatric CPET, but evaluation of their validity is lacking. The aim of
this study was to review pediatric CPET references values published
between 1980 and 2014. We specifically assessed the adequacy of the
normalization methods used to adjust for body size. Articles that
proposed references values were reviewed. We abstracted information on
exercise protocols, CPET measurements and normalization methods. We
then evaluated the studies’ methodological quality and assessed them
for potential biases. Thirty-four studies were included. We found
important heterogeneity in the choice of exercise protocols and in the
approach to adjustment for body size or other relevant confounding
factors. Adjustment for body size was principally done using linear
regression for age or weight. Assessment of potential biases (residual
association, heteroscedasticity and departure from the normal
distribution) was mentioned in only a minority of studies. Our study
shows that contemporary pediatric reference values for CPET have been
developed based on heterogeneous exercise protocols and variable
normalization strategies. Furthermore, assessment of potential bias has
been inconsistent and insufficiently described. High-quality reference
values with adequate adjustment for confounding variables are needed in
order to optimize CPET’s specificity and sensitivity to detect abnormal
cardiopulmonary response to exercise.

A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery.


Meybohm P, Bein B, Brosteanu O, Cremer J, Gruenewald M, Stoppe C, et al.

N Engl J Med. 2015;373(15):1397-407.

BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. METHODS: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. RESULTS: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed.

CONCLUSIONS: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery.

Feasibility of cardiopulmonary exercise testing and training using a robotics-assisted tilt table in dependent-ambulatory stroke patients

Saengsuwan, Jittima; Huber, Celine; Schreiber, Jonathan; Schuster-Amft,
Corina; Nef, Tobias; Hunt, Kenneth.

Journal of NeuroEngineering and Rehabilitation, December 2015, Vol. 12 Issue: Number 1 p1-10, 10p;

Abstract: We evaluated the feasibility of an augmented
robotics-assisted tilt table (RATT) for incremental cardiopulmonary
exercise testing (CPET) and exercise training in dependent-ambulatory
stroke patients.   Stroke patients (Functional Ambulation Category ≤ 3) underwent familiarization, an incremental
exercise test (IET) and a constant load test (CLT) on separate days. A
RATT equipped with force sensors in the thigh cuffs, a work rate
estimation algorithm and real-time visual feedback to guide the
exercise work rate was used. Feasibility assessment considered
technical feasibility, patient tolerability, and cardiopulmonary
responsiveness.  Eight patients (4 female) aged
58.3 ± 9.2 years (mean ± SD) were recruited and all completed the
study. For IETs, peak oxygen uptake (V’O2peak), peak heart rate
(HRpeak) and peak work rate (WRpeak) were 11.9 ± 4.0 ml/kg/min (45 % of
predicted V’O2max), 117 ± 32 beats/min (72 % of predicted HRmax) and
22.5 ± 13.0 W, respectively. Peak ratings of perceived exertion (RPE)
were on the range “hard” to “very hard”. All 8 patients reached their
limit of functional capacity in terms of either their cardiopulmonary
or neuromuscular performance.   A ventilatory threshold
(VT) was identified in 7 patients and a respiratory compensation point
(RCP) in 6 patients: mean V’O2at VT and RCP was 8.9 and 10.7 ml/kg/min,
respectively, which represent 75 % (VT) and 85 % (RCP) of mean
V’O2peak. Incremental CPET provided sufficient information to satisfy
the responsiveness criteria and identification of key outcomes in all 8
patients.  For CLTs, mean steady-state V’O2was
6.9 ml/kg/min (49 % of V’O2reserve), mean HR was 90 beats/min (56 % of
HRmax), RPEs were > 2, and all patients maintained the active work rate
for 10 min: these values meet recommended intensity levels for bouts of
training.  The augmented RATT is deemed feasible for
incremental cardiopulmonary exercise testing and exercise training in
dependent-ambulatory stroke patients: the approach was found to be
technically implementable, acceptable to the patients, and it showed
substantial cardiopulmonary responsiveness. This work has clinical
implications for patients with severe disability who otherwise are not
able to be tested.

Cardiopulmonary Exercise Testing to Detect Chronic Thromboembolic Pulmonary Hypertension in Patients with Normal Echocardiography

Matthias Held a Maria Grün a Regina Holl a Gudrun Hübner a Ralf Kaiser c
Sabine Karl b Martin Kolb e Hans Joachim Schäfers d Heinrike Wilkens c
Berthold Jany a
a Department of Internal Medicine, Medical Mission Hospital, Academic Teaching Hospital, and b Institute of
Mathematics, Julius Maximilian University of Würzburg, Würzburg , c Department of Internal Medicine V, Respiratory
and Critical Care Medicine, and d Clinic for Thoracic and Cardiovascular Surgery, University Hospital Homburg
Saar, Homburg , Germany; e Department of Medicine, Pathology and Molecular Medicine, Firestone Institute for
Respiratory Health, McMaster University, Hamilton, Ont. , Canada

Respiration 2014;87:379–387

Background: Chronic thromboembolic pulmonary hypertension
(CTEPH) is a serious complication of pulmonary embolism
(PE). Taking into account the reported incidence of
CTEPH after acute PE, the number of patients with undiagnosed
CTEPH may be high.
Objectives: We aimed to determine
if cardiopulmonary exercise testing (CPET) could serve
as complementary tool in the diagnosis of CTEPH and can
detect CTEPH in patients with normal echocardiography.
Methods: At diagnosis, we analyzed the data of CPET parameters
in 42 patients with proven CTEPH and 51 controls, and
evaluated the performance of two scores.
Results: V E /V CO 2
slope, EQ O 2 , EQ CO 2 , P(A-a) O 2 , end-tidal partial pressure of CO 2
at anaerobic threshold (PET CO 2 ) and capillary to end-tidal carbon
dioxide gradient [P(c-ET) CO 2 ] were significantly different
between patients with CTEPH and controls (p < 0.001). P(c-ET) CO 2 was
the single parameter with the highest sensitivity
(85.7%) and specificity (88.2%). A score combining V E /V CO 2
slope, P(A-a) O 2 , P(c-ET) CO 2 , PET CO 2 [4-parameter-CPET (4-PCPET)
score] reached a sensitivity of 83.3% and a specificity of
92.2% after cross-validation. In 42 patients with CTEPH, echocardiography
identified PH in 29 patients (69%), but it was
normal in 13 patients (31%). All patients with normal or unmeasurable
right ventricular systolic pressure had a pathological
CPET. Twelve of the 13 patients (92%) were detected
by both CPET scores.
Conclusion: CPET is a useful noninvasive
diagnostic tool for the detection of CTEPH in patients with
suspected PH but normal echocardiography. The 4-P-CPET
score provides a high sensitivity with the highest specificity.