Author + information
- Krischan D. Sjauw, MD,
- Maurice Remmelink, MD,
- Jan Baan Jr, MD, PhD,
- Kayan Lam, MD,
- Annemarie E. Engström, MD,
- René J. van der Schaaf, MD,
- Marije M. Vis, MD,
- Karel T. Koch, MD, PhD,
- Jan P. van Straalen, MSc,
- Jan G.P. Tijssen, PhD,
- Bas A.J.M. de Mol, MD, PhD,
- Robbert J. de Winter, MD, PhD,
- Jan J. Piek, MD, PhD and
- José P.S. Henriques, MD, PhD⁎ ()
- ↵⁎Department of Cardiology, Academic Medical Center—University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Amsterdam, the Netherlands
To the Editor: Unloading the left ventricle (LV) after ST-segment elevation myocardial infarction (STEMI) in addition to reperfusion therapy may reduce infarct size and may give the myocardium time to recuperate from ischemic stunning (1). This may be particularly true in STEMI patients with cardiogenic shock (CS) or pre-shock, who have a large ischemic area at risk for necrosis. Nowadays, intra-aortic counterpulsation (IABP) is the most accessible method of LV unloading and circulatory support. However, this treatment modality in randomized trials failed to show any benefit on infarct size, LV function, and/or mortality in the setting of STEMI. Nonetheless, mostly based on nonrandomized studies, IABP remains advocated and frequently used for hemodynamic stabilization in CS. True LV unloading with a left ventricular assist device (LVAD) might be superior to IABP therapy. The Impella LP2.5 (Abiomed Europe GmbH, Aachen, Germany) is a novel catheter-mounted (9-F) microaxial rotary blood pump (12-F) able to provide flow up to 2.5 l/min. It is inserted percutaneously through the femoral artery and positioned across the aortic valve in the LV. However, before initiation of a trial in STEMI patients with hemodynamic instability, the safety and feasibility of Impella support should be determined in hemodynamically less compromised patients.
From December 2005 until June 2006, a total of 20 consecutive patients were included in this single-center, nonrandomized pilot study (the AMC MACH [Academic Medical Center Mechanical support for Acute Congestive Heart failure in STEMI patients] 2 study), which was designed to evaluate the safety and feasibility of concomitant LV unloading with the Impella LP2.5 in STEMI. Eligible were all patients presenting with a first anterior STEMI within 6 h of symptom onset without CS treated with primary percutaneous coronary intervention (PCI). Immediately after PCI, 10 patients received 3 days of Impella support (Impella group). A concurrent group of 10 patients meeting all eligibility criteria were treated according to routine care, including IABP therapy as deemed necessary by the attending operator in 3 patients. All patients received optimal pharmacotherapy, including aspirin, beta-blocker, angiotensin-converting enzyme inhibitor, and statin therapy.
Continuous data are presented as mean ± standard deviation. Differences in continuous variables were assessed by the Mann-Whitney U test, in categorical variables by the chi-square test, and in paired comparisons by the Wilcoxon signed-rank test.
The primary safety and feasibility end points included device-related complications and major adverse cardiac and cerebral events during support and 4-month follow-up. The secondary objective, LV recovery, was assessed by echocardiography in an exploratory fashion to support our hypothesis and provide a more profound basis for further controlled trials.
Global left ventricular ejection fraction (LVEF) in both groups was determined on transthoracic echocardiography immediately after PCI (baseline), at 3 days (after Impella removal), and after 4 months. Baseline transthoracic echocardiography also served to assess the presence of LV mural thrombus, which is an exclusion criterion for Impella therapy. Finally, aortic regurgitation was assessed before, during, and after Impella support as well as at 4-month follow-up. Echocardiographic analyses were performed by an independent core laboratory (DCRI, Duke University, Durham, North Carolina).
The patient characteristics at first glance show no significant differences between the groups (Table 1). However, in the Impella group there is a trend toward higher scores on most conventional risk factors, admission laboratory values, and indexes of extent of myocardial necrosis, indicating a worse clinical condition at baseline.
Impella insertion was successful in all cases. Median time for pump placement was 11 min. After subsequent maximization of pump performance (maximum flow 2.2 ± 0.1 l/min; mean ± standard error of the mean), an immediate increase in cardiac output (4.4 ± 0.3 l/min to 4.9 ± 0.5 l/min, n = 5, p = NS) and a decrease in pulmonary capillary wedge pressure (24.3 ± 2.4 mm Hg to 17.3 ± 0.4 mm Hg, n = 5, p < 0.05) was observed. Weaning was commenced from 48 to 72 h. Median assist time was 71 h and 43 min. During Impella support no signs or increase by ≥1 grade of aortic regurgitation were observed; neither were any late adverse effects on the aortic valve at 4-month follow-up. Groin bleeding requiring transfusion (mainly oozing along femoral sheath) was observed in 4 patients in the Impella group compared with 2 in the control group; however, after implementing a more strict institutional heparin protocol, oozing was not an important issue. Hemolysis (free-hemoglobin levels >10 mg/dl) occurred only within the first 24 h of support, returning quickly toward normal levels. There were no other device-related adverse events, nor major adverse cardiac and cerebral events (death, repeat myocardial infarction, target vessel revascularization, stroke) during and after Impella support.
Changes in LVEF from baseline (immediately after PCI) to 3-day (Impella removal) and 4-month follow-up are shown in Figure 1 (vertical bars show mean values ± standard error of the mean for paired data). In the Impella group (n = 8), LVEF improved from 28% at baseline to 37% (p < 0.05) and 41% (p < 0.05) after respectively 3 days and 4 months, whereas in the control group (n = 9) no significant improvement was observed; LVEF changed from 40% to respectively 42% (p = NS) and 45% (p = NS).
We previously showed the safety and feasibility of periprocedural LV support with the Impella LP2.5 in elective high-risk PCI patients (2) (the AMC MACH1 study). The presented pilot study in STEMI patients without hemodynamic compromise extends this safety and feasibility to concomitant LV support during 3 days with Impella LP2.5. Severe complications, such as major bleeding, vascular injury, thromboembolism, and major hemolysis, often accompanying miniaturized LVADs, did not occur in our study. Furthermore, the Impella showed to be easily implantable and provided an increase of cardiac output and a decrease of LV end-diastolic pressure. We previously showed that the Impella LP2.5 improves intracoronary perfusion pressure, coronary flow velocity reserve, and microvascular resistance (3).
Most interestingly we observed a marked LV recovery in the Impella group, suggesting a possible beneficial effect of mechanical unloading on postinfarct adverse remodeling.
The extent of this effect is more than could be expected after optimal reperfusion combined with optimal postinfarction pharmacotherapy. Functional recovery occurs in a significant proportion of patients because of contemporary STEMI treatment. Reported increases in LVEF from baseline within 24 h after PCI up to 6 months range from 3 LVEF percentage points to 4.5 LVEF percentage points, comparable with the improvement observed in our control group (4,5). However, this is considerably less compared with the 9 LVEF percentage points and 13 LVEF percentage points improvement observed after respectively 3 days and 4 months in the Impella group.
In conclusion, the findings concerning the safety and feasibility of prolonged Impella LP2.5 support in the setting of STEMI are encouraging. Furthermore, LV unloading resulted in an unexpected acute and sustained LV recovery compared with routine-care patients. These findings should be seen as the first explorative findings in humans and an incentive for larger-scale studies. Percutaneous LVAD therapy may prove to be a promising alternative for the passive support offered by IABP. We recently initiated a head-to-head randomized comparison of IABP and Impella support in hemodynamically compromised patients with large anterior STEMI.
Please note: Dr. Henriques has received an unrestricted educational research grant from Abiomed Europe GmbH, Aachen, Germany.
- American College of Cardiology Foundation
- Smalling R.W.,
- Cassidy D.B.,
- Barrett R.,
- et al.