Category Archives: Publications

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.

Pulmonale Hypertonie bei Lungen- und Linksherzerkrankungen

Held, M.; Rosenkranz, S.

Der Pneumologe, September 2015, Vol. 12 Issue:
Number 5 p410-416, 7p;

Increasing awareness of pulmonary hypertension (PH) leads to
an increased detection rate even in elderly patients with a higher rate
of comorbidities. In patients with PH and left-sided heart or pulmonary
diseases it is necessary to assess if these cardiac or pulmonary
conditions are the cause of PH or only independent comorbidities.
Additionally, it has to be evaluated if a chronic left-sided
ventricular disease with pulmonary congestion has induced a pulmonary
vasculopathy with severe PH. Sleep apnea syndrome can underlie PH and
severe PH can lead to central sleep apnea. These aspects require
experience and a careful and extensive diagnostic evaluation, including
complete hemodynamic assessment, imaging techniques, lung function and
cardiopulmonary exercise testing. Experienced PH centers should be
involved in this diagnostic process at an early stage. Although PH
leads to a worsening of the prognosis of pulmonary fibrosis and chronic
obstructive pulmonary disease (COPD) as well as of diastolic and
systolic heart failure, published data do not support targeted PH
therapies under these conditions due to a lack of evidence. Therefore,
the treatment of the underlying disease is the primary goal. Mitral
valve repair and non-invasive pressure ventilation in patients with
alveolar hypoventilation lead to hemodynamic and functional
improvement. Patients with PH and left heart disease show improvement
following normalization of volume load. So far there are no approved
medical therapies for PH due to left-sided heart disease and PH due to
lung diseases. Patients with PH and left-sided heart diseases and lung
diseases should be introduced in specific clinical studies.;

Pulmonary capillary hemangiomatosis: the role of invasive cardiopulmonary exercise testing

DuBrock, Hilary M.; Kradin, Richard
L.; Rodriguez-Lopez, Josanna M.; Channick, Richard N..

Pulmonary Circulation (JSTOR), September 2015, Vol. 5 Issue: Number 3 p580-586,

Abstract: Pulmonary capillary hemangiomatosis (PCH) is a
rare form of pulmonary arterial hypertension (PAH) characterized by
pulmonary capillary proliferation and pseudoinvasion of collagenous
septal structures. PCH is often accompanied by veno-occlusive changes
and pulmonary hypertensive arterial remodeling. The clinical and
pathological diagnosis of PCH can be subtle and easily missed. Most
reported cases of PCH have been associated with resting PAH. We report
the cases of 3 patients who initially presented with exertional dyspnea
with normal to mildly elevated resting pulmonary arterial pressures and
marked intrapulmonary shunting. In all 3 patients, invasive
cardiopulmonary exercise testing was suggestive of pulmonary vascular
disease. Owing to abnormalities on invasive exercise testing, lung
biopsies were performed; these were diagnostic of PCH, and the patients
were referred for lung transplantation. We describe unique features of
these 3 cases—including novel pathological findings and the presence of
intrapulmonary shunting in all 3 patients—and we discuss the role of
cardiopulmonary exercise testing in the evaluation of PCH.

Association of Chronic Kidney Disease With Chronotropic Incompetence in Heart Failure With Preserved Ejection Fraction

Klein, David A.;
Katz, Daniel H.; Beussink-Nelson, Lauren; Sanchez, Cynthia L.;
Strzelczyk, Theresa A.; Shah, Sanjiv J..

The American Journal of Cardiology, October 2015, Vol. 116 Issue: Number 7 p1093-1100, 8p

Abstract: Chronotropic incompetence (CI) is common in heart failure
with preserved ejection fraction (HFpEF) and may be a key reason
underlying exercise intolerance in these patients. However, the
determinants of CI in HFpEF are unknown. We prospectively studied 157
patients with consecutive HFpEF who underwent cardiopulmonary exercise
testing and defined CI according to specific thresholds of the percent
heart rate reserve (%HRR). CI was diagnosed as present if %HRR <80 if
not taking a β blocker and <62 if taking β blockers. Participants who
achieved inadequate exercise effort (respiratory exchange ratio ≤1.05)
on cardiopulmonary exercise testing were excluded.
Multivariable-adjusted logistic regression was used to determine the
factors associated with CI. Of the 157 participants, 108 (69%) achieved
a respiratory exchange ratio >1.05 and were included in the final
analysis. Of these 108 participants, 70% were women, 62% were taking β
blockers, and 38% had chronic kidney disease. Most patients with HFpEF
met criteria for CI (81 of 108; 75%). Lower estimated glomerular
filtration rate (GFR), higher B-type natriuretic peptide, and higher
pulmonary artery systolic pressure were each associated with CI. A 1-SD
decrease in GFR was independently associated with CI after
multivariable adjustment (adjusted odds ratio 2.2, 95% confidence
interval 1.1 to 4.4, p = 0.02). The association between reduced GFR and
CI persisted when considering a variety of measures of chronotropic
response. In conclusion, reduced GFR is the major clinical correlate of
CI in patients with HFpEF, and further study of the relation between
chronic kidney disease and CI may provide insight into the
pathophysiology of CI in HFpEF.

Comprehensive Analysis of Cardiopulmonary Exercise Testing and Mortality in Patients With Systolic Heart Failure

The Henry Ford Hospital Cardiopulmonary Exercise Testing (FIT-CPX) Project by Brawner,
Clinton A.; Shafiq, Ali; Aldred, Heather A.; Ehrman, Jonathan K.;
Leifer, Eric S.; Selektor, Yelena; Tita, Cristina; Velez, Mauricio;
Williams, Celeste T.; Schairer, John R.; Lanfear, David E.; Keteyian,
Steven J..

Journal of Cardiac Failure, September 2015, Vol. 21 Issue:
Number 9 p710-718, 9p;

Abstract: Many studies have shown a strong
association between numerous variables from a cardiopulmonary exercise
(CPX) test and prognosis in patients with heart failure with reduced
ejection fraction (HFrEF). However, few studies have compared the
prognostic value of a majority of these variables simultaneously, so
controversy remains regarding optimal interpretation.

Clinical assessment before hepatectomy identifies high-risk patients

Ulyett, Simon; Wiggans, Matthew G.; Bowles, Matthew J.; Aroori,
Somaiah; Briggs, Christopher D.; Erasmus, Paul; Minto, Gary; Stell,
David A..

Journal of Surgical Research, September 2015, Vol. 198 Issue:
Number 1 p87-92, 6p;

Abstract: Liver resection is associated with
significant morbidity, and assessment of risk is an important part of
preoperative consultations. Objective methods exist to assess operative
risk, including cardiopulmonary exercise testing (CPX). Subjective
assessment is also made in clinic, and patients perceived to be
high-risk are referred for CPX at our institution. This article
addresses clinicians’ ability to identify patients with a higher risk
of surgical complications after hepatectomy, using selection for CPX as
a surrogate marker for increased operative risk.;

The Effect of beta-blockade on objectively measured physical fitness in patients with abdominal aortic aneurysms–A blinded interventional study.

West MA; Parry M; Asher R; Key A; Walker P;
Loughney L; Pintus S; Duffy N; Jack S; Torella F

British Journal Of Anaesthesia [Br J Anaesth], ISSN: 1471-6771, 2015 Jun; Vol. 114 (6),
pp. 878-85; Publisher: Oxford University Press; PMID: 25716221;

Background: Perioperative beta-blockade is widely used, especially
before vascular surgery; however, its impact on exercise performance
assessed using cardiopulmonary exercise testing (CPET) in this group is
unknown. We hypothesized that beta-blocker therapy would significantly
improve CPET-derived physical fitness in this group.Methods: We
recruited patients with abdominal aortic aneurysms (AAA) of <5.5 cm
under surveillance. All patients underwent CPET on and off
beta-blockers. Patients routinely prescribed beta-blockers underwent a
first CPET on medication. Beta-blockers were stopped for one week
before a second CPET. Patients not routinely taking beta-blockers
underwent the first CPET off treatment, then performed a second CPET
after commencement of bisoprolol for at least 48 h. Oxygen uptake
(.VO2) at estimated lactate threshold and .VO2 at peak were primary
outcome variables. A linear mixed-effects model was fitted to
investigate any difference in adjusted CPET variables on and off
beta-blockers.Results: Forty-eight patients completed the study. No
difference was observed in .VO2 at estimated lactate threshold and .VO2
at peak; however, a significant decrease in .VE/.VCO2 at estimated
lactate threshold and peak, an increase in workload at estimated
lactate threshold., O2 pulse and heart rate both at estimated lactate
threshold and peak was found with beta-blockers. Patients taking
beta-blockers routinely (chronic group) had worse exercise performance
(lower .VO2 ).

Conclusions: Beta blockade has a significant impact on
CPET-derived exercise performance, albeit without changing .VO2 at
estimated lactate threshold and.VO2 at peak. This supports performance
of preoperative CPET on or off beta-blockers depending on local
perioperative practice.Clinical Trial Registration: NCT 02106286.

Prediction of organ-specific complications following abdominal aortic aneurysm repair using cardiopulmonary exercise testing.

Barakat HM; Shahin Y; McCollum PT; Chetter IC,

ISSN: 1365-2044, 2015 Jun; Vol. 70 (6), pp. 679-85;
Publisher: Wiley-Blackwell; PMID: 25656939;

This study aimed at
assessing whether measures of aerobic fitness can predict postoperative
cardiac and pulmonary complications, 30-day mortality and length of
hospital stay following elective abdominal aortic aneurysm repair. We
prospectively collected cardiopulmonary exercise testing data over two
years for 130 patients. Upon multivariate analysis, a decreased
anaerobic threshold (OR (95% CI) 0.55 (0.37-0.84); p = 0.005) and open
repair (OR (95% CI) 6.99 (1.56-31.48); p = 0.011) were associated with
cardiac complications. Similarly, an increased ventilatory equivalent
for carbon dioxide (OR (95% CI) 1.18 (1.05-1.33); p = 0.005) and open
repair (OR (95% CI) 14.29 (3.24-62.90); p < 0.001) were associated with
pulmonary complications. Patients who had an endovascular repair had
shorter hospital and critical care lengths of stay (p < 0.001).
Measures of fitness were not associated with 30-day mortality or length
of hospital stay. Cardiopulmonary exercise testing variables,
therefore, seem to predict different postoperative complications
following abdominal aortic aneurysm repair, which adds value to their
routine use in risk stratification and optimisation of peri-operative
care.© 2015 The Association of Anaesthetists of Great Britain and

Right Ventricular Mass is Associated with Exercise Capacity in Adults with Repaired Tetralogy of Fallot

O’Meagher, Shamus; Seneviratne,
Martin; Skilton, Michael; Munoz, Phillip; Robinson, Peter; Malitz,
Nathan; Tanous, David; Celermajer, David; Puranik, Rajesh.

Pediatric Cardiology, August 2015, Vol. 36 Issue: Number 6 p1225-1231, 7p;
Abstract: The relationship between exercise capacity and right
ventricular (RV) structure and function in adult repaired tetralogy of
Fallot (TOF) is poorly understood. We therefore aimed to examine the
relationships between cardiac MRI and cardiopulmonary exercise test
variables in adult repaired TOF patients. In particular, we sought to
determine the role of RV mass in determining exercise capacity.
Eighty-two adult repaired TOF patients (age at evaluation
26 ± 10 years; mean age at repair 2.5 ± 2.8 years; 23.3 ± 7.9 years
since repair; 53 males) (including nine patients with tetralogy-type
pulmonary atresia with ventricular septal defect) were prospectively
recruited to undergo cardiac MRI and cardiopulmonary exercise testing.
As expected, these repaired TOF patients had RV dilatation (indexed RV
end-diastolic volume: 153 ± 43.9 mL/m2), moderate–severe pulmonary
regurgitation (pulmonary regurgitant fraction: 33 ± 14 %) and preserved
left (LV ejection fraction: 59 ± 8 %) and RV systolic function (RV
ejection fraction: 51 ± 7 %). Exercise capacity was near-normal (peak
work: 88 ± 17 % predicted; peak oxygen consumption: 84 ± 17 %
predicted). Peak work exhibited a significant positive correlation with
RV mass in univariate analysis (r= 0.45, p< 0.001) and (independent of
other cardiac MRI variables) in multivariate analyses. For each 10 g
higher RV mass, peak work was 8 W higher. Peak work exhibits a
significant positive correlation with RV mass, independent of other
cardiac MRI variables. RV mass measured on cardiac MRI may provide a
novel marker of clinical progress in adult patients with repaired TOF.