Category Archives: Publications

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.

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.