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Online Appendix for the following November 4 JACC article
TITLE: A Randomized Clinical Trial to Evaluate the Safety and Efficacy of a Percutaneous
Left Ventricular Assist Device (Impella LP2.5) Versus Intra-Aortic Balloon Pumping For
Treatment of Cardiogenic Shock Caused by Myocardial Infarction
AUTHORS: Melchior Seyfarth, MD, Dirk Sibbing, MD, Iris Bauer, MS, Georg Fröhlich,
MD, Lorenz Bott-Flügel MD, Robert Byrne MB, MRCPI, Josef Dirschinger, MD, Adnan
Kastrati, MD, Albert Schömig, MD
APPENDIX
Patient Population
Eligible participants for this study were patients with: 1) acute myocardial infarction (AMI)
<48 h, confirmed by ischemic symptoms for at least 30 min with elevated cardiac markers or
ST-segment elevation or left bundle branch block. An AMI was suspected when patients
were resuscitated and cardiac markers and/or electrocardiographic changes met criteria for
AMI/acute coronary syndrome; 2) Cardiogenic shock was defined using both clinical and
hemodynamic criteria as previously described in the SHOCK trial (1). In brief, clinical
criteria were hypotension (systolic blood pressure <90 mm Hg) and a heart rate >90
beats/min or the need for positive inotropic drugs to maintain a systolic blood pressure >90
mm Hg and end-organ hypoperfusion (cool extremities or a urine output of <30 ml/h) or
pulmonary edema. Hemodynamic criteria were either a cardiac index of no more than 2.2
l/min per square meter of body surface area and a pulmonary capillary wedge pressure >15
mm Hg or an angiographically measured left ventricular ejection fraction <30% and left
ventricular end diastolic pressure >20 mm Hg. The onset of shock had to be within 24 h.
Exclusion criteria were specified as: age <18 years; prolonged resuscitation (>30
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min); hypertrophic obstructive cardiomyopathy; definite thrombus in left ventricle; treatment
with intra-aortic balloon pump; severe valvular disease or mechanical heart valve;
cardiogenic shock caused by mechanical complications of AMI such as ventricular septal
defect, acute mitral regurgitation greater than second degree, or rupture of the ventricle;
predominant right ventricular failure or the need for a right ventricular assist device; sepsis;
known cerebral disease; bleeding with a need for surgical intervention; pulmonary embolism;
allergy to heparin or any known coagulopathy; aortic regurgitation greater than second
degree; pregnancy; or inclusion in another study or trial.
The study was performed in Germany between September 2004 and January 2007.
Statistical Analysis
The primary end point of the study was the hemodynamic improvement within 30 min after
implantation defined as the increase in cardiac index from baseline. We applied a modified
intention-to-treat principle because 1 patient could not be included in the analysis because of
unavailability of the assigned device after enrollment. For patients not surviving to the time
point for primary end point calculation, we performed 2 kinds of analysis by first assuming a
null effect of the device and second assuming an effect equal to the worst hemodynamic
effect in the group. Because only 1 patient died before implantation (Impella group), we were
able to analyze the primary end point by including this patient in different ways, none of
which affected the statistical differences in the data. Secondary end points of the study were
hemodynamic and metabolic parameters every second hour during the first 6 h and every
eighth hour as long as the device was implanted; all-cause mortality at 30 days; devicerelated complications including hemolysis, major bleeding, cerebrovascular events, and limb
ischemia; and multiple-organ dysfunction scores at 30 days using Multiple Organ
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Dysfunction Score and Sepsis-related Organ Failure Assessment criteria (2,3). With a sample
size of 26 patients, we achieved 80% power to detect a significant enhancement of cardiac
index from +0.15 l/min in patients with intra-aortic balloon pump to +0.50 l/min in patients
with Impella LP2.5 at an α level of 0.05.
Hemodynamic parameters (arterial pressure, pulmonary arterial pressure, right atrial
pressure, pulmonary capillary wedge pressure, cardiac index, cardiac output, heart rate,
systemic vascular resistance) were analyzed as mean ± SD. Additionally, cardiac power
index (CPI) was calculated as CI × mean arterial pressure × 0.0022 (4). For patients with
augmentation of the Impella LP2.5 device, endogenous CPI of the left ventricle was
calculated as CPILV = CPItotal − CPIImpella. The CPIImpella value was based on the actual pump
flow of the device. Patient data are presented as mean ± SD, continuous variables as median
and interquartile range, and categorical variables as counts and proportions (%). Data were
presented as median and interquartile range when parametric assumptions were inappropriate
(e.g., serum levels of free hemoglobin). Differences between the groups were tested with the
use of 2-tailed t test for parametric variables and Mann-Whitney U tests for continuous data,
χ2 test or Fisher exact test for categorical data as appropriate, and were considered as being
statistically significant at a 2-sided value of p < 0.05. Analysis of survival (Kaplan-Meier
method) was performed using the Log-rank test. All statistical analyses were performed with
SPSS software (SPSS Inc., Chicago, Illinois).
References
1. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial
infarction complicated by cardiogenic shock. SHOCK Investigators. Should we emergently
revascularize occluded coronaries for cardiogenic shock. N Engl J Med 1999;341:625–34.
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2. Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple organ
dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med
1995;23:1638–52.
3. Vincent JL, Moreno R, Takala J, et al., on behalf of the Working Group on Sepsis-Related
Problems of the European Society of Intensive Care Medicine. The SOFA (Sepsis-related
Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med.
1996;22:707–10.
4. Cotter G, Moshkovitz Y, Kaluski E, et al. The role of cardiac power and systemic vascular
resistance in the pathophysiology and diagnosis of patients with acute congestive heart failure.
Eur J Heart Fail 2003;5:443–51.
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