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Trajectories of cardiac function following treatment with Impella in patients with acute anterior ST-elevation myocardial infarction

Open AccessPublished:November 04, 2022DOI:https://doi.org/10.1016/j.cjco.2022.11.002

      Abstract

      Background

      Left ventricular (LV) unloading using the percutaneous micro-axial pump Impella is increasingly used in patients with anterior ST-segment elevation myocardial infarction (STEMI) and overt cardiogenic shock. In this context, the evolution of cardiac function and dimensions beyond hospital discharge remains uncertain. We aimed to characterize echocardiographic changes over time in patients with acute anterior STEMI treated with Impella.

      Methods

      From an ongoing prospective registry, consecutive patients with acute anterior STEMI managed with an Impella device were extracted. Transthoracic echocardiography was performed at index hospitalization and at first outpatient follow-up. Predictors of response, defined as a ≥ 10% absolute increase in left ventricular ejection fraction (LVEF) at follow-up, were sought.

      Results

      A total of 66 patients (89.4% male, 64.3±11.6 years) with anterior STEMI were treated with Impella in the first 24 hours of hospitalization from 2014 to 2022. In-hospital mortality was 24%. Major bleeding and vascular complications requiring surgery occurred in 24% and 11% of patients, respectively. At baseline, mean LVEF was 34 ±12%. At follow-up, survivors showed a significant increase in LVEF (p <0.0001), whilst LV dimensions, diastolic parameters, and measures of right ventricular dimension and function remained stable. Overall, 28 patients had a ≥10% absolute increase in LVEF at follow-up. Baseline creatinine was the only significant predictor of response at univariate analysis.

      Conclusions

      Among patients with anterior STEMI requiring mechanical hemodynamic support with Impella, the majority of survivors showed a sustaining increase in LV function, without evidence of adverse remodeling. This signal warrants further investigation in dedicated trials.

      Graphical abstract

      Keywords

      INTRODUCTION

      Patients presenting with acute anterior ST-segment myocardial infarction (STEMI) and beginning or overt cardiogenic shock still show a very high morbidity and mortality rate.

      Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European Heart Journal. 2018;39(2):119-177. doi:10.1093/eurheartj/ehx393

      ,
      • Zeymer U.
      • Bueno H.
      • Granger C.B.
      • et al.
      Acute Cardiovascular Care Association position statement for the diagnosis and treatment of patients with acute myocardial infarction complicated by cardiogenic shock: A document of the Acute Cardiovascular Care Association of the European Society of Cardiology.
      Considering the rapid and potentially lethal downward spiral of myocardial ischemia and related systemic organ dysfunction, early identification and treatment are crucial to increase chances of survival.
      The contemporary management of STEMI-associated cardiogenic shock focuses on treating the underlying cause by prompt revascularization of the culprit vessel,3 as well as hemodynamic stabilization by means of pharmacological therapy, mechanical ventilation, and mechanical circulatory support (MCS) in patients not responding to standard treatment.2
      The Impella device (Abiomed, Danvers, Massachusetts) is a percutaneously delivered MCS that unloads the left ventricle (LV) by pumping blood from the LV to the aorta.
      • Meyns B.
      • Stolinski J.
      • Leunens V.
      • Verbeken E.
      • Flameng W.
      Left ventricular support by Catheter-Mountedaxial flow pump reduces infarct size.
      ,
      • Attinger-Toller A.
      • Bossard M.
      • Cioffi G.M.
      • et al.
      Ventricular Unloading Using the ImpellaTM Device in Cardiogenic Shock.
      As a result, Impella reduces LV end-diastolic volume (LVEDV) and pressure (LVEDP), leading to a reduction of myocardial wall tension and workload, both of which diminish myocardial oxygen demand.
      • Attinger-Toller A.
      • Bossard M.
      • Cioffi G.M.
      • et al.
      Ventricular Unloading Using the ImpellaTM Device in Cardiogenic Shock.
      ,
      • Valgimigli M.
      • Steendijk P.
      • Sianos G.
      • Onderwater E.
      • Serruys P.W.
      Left ventricular unloading and concomitant total cardiac output increase by the use of percutaneous impella recover LP 2.5 assist device during high-risk coronary intervention: Impella Assist Device in High-Risk PCI.
      Experimental studies suggested that early LV unloading in the setting of an acute myocardial infarction (MI) reduces infarct size.
      • Esposito M.L.
      • Zhang Y.
      • Qiao X.
      • et al.
      Left Ventricular Unloading Before Reperfusion Promotes Functional Recovery After Acute Myocardial Infarction.
      • Kapur N.K.
      • Paruchuri V.
      • Urbano-Morales J.A.
      • et al.
      Mechanically Unloading the Left Ventricle Before Coronary Reperfusion Reduces Left Ventricular Wall Stress and Myocardial Infarct Size.
      • Saku K.
      • Kakino T.
      • Arimura T.
      • et al.
      Left Ventricular Mechanical Unloading by Total Support of Impella in Myocardial Infarction Reduces Infarct Size, Preserves Left Ventricular Function, and Prevents Subsequent Heart Failure in Dogs.
      However, the impact of ventricular unloading with the Impella device on cardiac remodeling in patients with acute anterior STEMI complicated by cardiogenic shock is still largely unknown.
      The purpose of the present study was to describe the time course of cardiac function and remodeling after acute anterior STEMI treated with the Impella device.

      METHODS

      Study population and data collection

      From an ongoing MCS registry (ClinicalTrials.gov Identifier: NCT04117230), we analyzed consecutive patients older than 18 years of age at the Heart Center of the Luzerner Kantonsspital, Lucerne, Switzerland, which represents the tertiary cardiology facility of the Central Part of Switzerland, between December 2014 and February 2022.
      The inclusion criteria were: 1) acute (defined as onset of symptoms within 24 hours) anterior STEMI; 2) implantation of left-heart Impella within 24 hours from STEMI diagnosis. Patients presenting with non-anterior STEMI localization, as well as subacute STEMI (i.e. time from pain onset to diagnosis > 24h), or receiving another type of MCS, were excluded. All patients were treated according to current STEMI guidelines, thus receiving a coronary angiography and a primary percutaneous coronary intervention (PCI) to the culprit vessel.

      Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European Heart Journal. 2018;39(2):119-177. doi:10.1093/eurheartj/ehx393

      ,
      • Steg PhG.
      • James S.K.
      • Atar D.
      • et al.
      ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation.
      All baseline coronary angiograms were independently analyzed by two senior invasive cardiologists (AAT and MB). Data on demographics, previous history, cardiovascular risk factors, angiography, laboratory tests, and discharge medications were collected by study personal and entered in a dedicated database on REDCap (version 11.1.27).
      • Harris P.A.
      • Taylor R.
      • Thielke R.
      • Payne J.
      • Gonzalez N.
      • Conde J.G.
      Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support.
      Prospective data acquisition after enrollment was approved by the local and national ethics committee (EKNZ/ Swissethics, BASEC-ID 2019-00274) and conducted according to the principles of the Declaration of Helsinki.

      Impella implantation

      The catheter-based, continuous microaxial flow pumps Impella 2.5 and CP can be implanted fully percutaneously, generally through the femoral artery.
      • Balthazar T.
      • Vandenbriele C.
      • Verbrugge F.H.
      • et al.
      Managing Patients With Short-Term Mechanical Circulatory Support.
      The indication for Impella implantation was given case-by-case by the treating invasive cardiologist performing the coronary angiography.
      As part of our clinical routine, we obtained a contrast angiogram in an ipsilateral projection to assess puncture height and anatomical suitability of the iliac and femoral arteries prior to Impella insertion. Ultrasound guidance was used, whenever possible. All patients were anticoagulated with unfractionated heparin to achieve an activated clotting time >250s during PCI. Finally, the Impella devices were inserted over a stiff 0.018-inch guide wire, advanced under fluoroscopy and positioned in a retrograde fashion across the aortic valve.
      The timing of Impella insertion generally followed two principles: (1) implantation of the device and establishing LV unloading prior to PCI and ensuring continuous support during and following PCI. This represents the preferred approach for patients presenting with established and profound cardiogenic shock; (2) device implantation after primary PCI; this strategy is generally pursued in patients showing growing inotrope-dependency, deteriorating hemodynamics and/ or signs of multiorgan dysfunction secondary to advancing cardiogenic shock, which worsens following revascularization. In all patients, the decision for Impella removal was made after interdisciplinary evaluation by the interventional cardiologists and critical care physicians, based on three main criteria: 1) no hemodynamic support needed anymore after appropriate weaning, 2) escalation of support (i.e., extra-corporeal membrane oxygenation, left ventricular assist device [LVAD]) or heart transplantation), 3) withdrawal of therapy and/or patient death.

      Echocardiography

      Transthoracic echocardiography (TTE) was performed at index hospitalization (baseline) and at outpatient follow-up. Baseline echocardiography followed the standard protocol in our center and was performed by a board cardiologist either in ICU (Affinity or CX50, Philips Healthcare, The Netherlands) or in our echocardiography laboratory (EPIQ 7, Philips Healthcare, The Netherlands, or VIVID E95, GE Healthcare, USA). If more than one TTE was performed during hospitalization, only the first one after STEMI diagnosis was taken into consideration for the analysis. Follow-up echocardiograms were performed either in our outpatient clinic or by external cardiologists. All echocardiograms were reviewed offline using a dedicated software package (Intellispace, Philips Healthcare, The Netherlands) by an independent physician certified in TTE by the European Association of Cardiovascular Imaging (EACVI). Echocardiographic measures were performed according to EACVI guidelines.
      • Lang R.M.
      • Badano L.P.
      • Mor-Avi V.
      • et al.
      Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.

      Statistical analysis

      Variables are presented as mean±standard deviation or median [1st-3rd quartile], depending on their distribution. Normality of distribution was assessed using the Shapiro-Wilk test and a Q-Q plot. Categorical variables are presented as number (percentage). Continuous variables were compared using Student’s t test or Wilcoxon’s Signed Rank test, depending on distribution. Categorical variables were compared using Fisher’s exact test. In patients who survived and had echocardiographic follow-up within the first months after discharge, we compared baseline and first follow-up echocardiographic data. According to previous literature, which showed a LVEF absolute increase ≥10% after MI being prognostically significant,
      • Chew D.S.
      • Heikki H.
      • Schmidt G.
      • et al.
      Change in Left Ventricular Ejection Fraction Following First Myocardial Infarction and Outcome.
      we stratified patients based on LVEF improvement at follow-up. After dividing patients in responders (difference in LVEF between 1st follow-up and baseline ≥ 10%) and non-responders, we compared the two groups for variables known to be associated with prognosis. We performed no imputation for missing data. Variables were compared when less than 20% of data were missing. Two-sided p values less than 0.05 were considered statistically significant. JMP Pro (Version 16, SAS Institute Inc., Cary, NC, 1989–2021) was used for data quality assessment, statistical analysis, and graphical representation.

      RESULTS

      Overall, 66 consecutive patients with the prespecified inclusion criteria were included. Those patients had been treated between December 2014 and February 2022. The patient inclusion flowchart is shown in Figure 1.
      Figure thumbnail gr1
      Figure 1STROBE study flowchart., MCS, mechanical circulatory support; STEMI, ST-elevation myocardial infarction

      Baseline characteristics

      The baseline characteristics are displayed in Table 1 and Supplemental Table S1. Our cohort’s mean age was 64±12 years and 89% were male. Known coronary artery disease (CAD) was present in 18% of patients. Among cardiovascular risk factors, smoking (47%) and arterial hypertension (52%) were common. Approximately one third of all patients presented with out-of-hospital cardiac arrest (OHCA) and 79% were in profound cardiogenic shock (SCAI class C, D or E).
      Table 1Baseline characteristics.
      All patients (n=66)
      Age, years64.3 (11.6)
      Male, n (%)59 (89.4)
      BMI, kg/m224.9 [24.2 – 28.1]
      Comorbidities
      CAD, n (%)12 (18.2)
      Previous MI, n (%)9 (13.6)
      Previous PCI, n (%)10 (15.2)
      Previous CABG, n (%)1 (1.5)
      Heart failure, n (%)2 (3.0)
      Atrial fibrillation, n (%)2 (3.0)
      Previous stroke, n (%)3 (4.5)
      PAD, n (%)7 (10.6)
      CKD (eGFR <30 ml/min/1.73), n (%)3 (4.5)
      Cardiovascular risk factors
      Smoking, n (%)31 (47.0)
      Arterial hypertension, n (%)34 (51.5)
      Dyslipidemia, n (%)25 (37.9)
      Diabetes mellitus, n (%)8 (12.1)
      Family history of CAD, n (%)11 (16.6)
      Clinical presentation
      OHCA, n (%)25 (37.3)
      Profound cardiogenic shock*, n (%)52 (78.8)
      SCAI class at admission
      A, n (%)12 (18.2)
      B, n (%)2 (3.0)
      C, n (%)8 (12.1)
      D, n (%)19 (28.8)
      E, n (%)25 (37.9)
      GRACE score, points182 ±25
      CardSHOCK score, points3 [2 – 4]
      BMI, body mass index; CABG, coronary artery bypass graft surgery; CAD, coronary artery disease; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; MI, myocardial infarction; OHCA, out-of-hospital cardiac arrest; PAD, peripheral artery disease; PCI, percutaneous coronary intervention.
      *defined as SCAI class C, D or E.

      In-hospital management and clinical outcomes

      In-hospital management is summarized in Table 2 and Supplemental Table S2. Except for one patient who died before angioplasty, all patients were treated with primary PCI. No patient received thrombolysis. Most patients (96%) were implanted with an Impella CP. The median duration of Impella support was 33 [23; 51] hours. Six patients received a second device, which was intra-aortic balloon pump (IABP) through the contralateral femoral artery in all cases, in the first hours or days after Impella implantation. Among these, five received concomitant use of Impella and IABP, and in one patient Impella was explanted previous IABP implantation. Thirty-three (50%) patients required mechanical ventilation. The median stay in intensive care unit (ICU) was 4 [2 – 10] days. In-hospital mortality was 24% (n=16), mainly due to cardiac causes (i.e., refractory cardiogenic shock or resuscitation). The outcomes are summarized in Table 3.
      Table 2In-hospital management.
      All patients (n=66)
      Type of support
      Impella 2.5, n (%)3 (4.5)
      Impella CP, n (%)63 (95.5)
      Timing of support
      Before PCI, n (%)49 (74.2)
      After PCI, n (%)16 (24.2)
      Indication for Impella
      Cardiac arrest, n (%)37 (56.1)
      Profound cardiogenic shock (at least SCAI class C), n (%)63 (95.5)
      Beginning cardiogenic shock (SCAI class B), n (%)3 (4.5)
      Other MCS device, n (%)
      Impella and IABP combined, n (%)5 (7.6)
      IABP after Impella explantation, n (%)1 (1.5)
      LVEDP at implantation, mmHg31.7 ± 9.5
      MAP at implantation, mmHg70 [59.0 – 90.0]
      Ongoing resuscitation during implantation, n (%)9 (13.6)
      Duration of support, hrs32.7 [23 – 50.5]
      PCI performed, n (%)65 (98.5)
      Culprit vessel
      LM, n (%)13 (19.7)
      LAD, n (%)53 (80.3)
      ICU stay, days4 [2-10]
      Mechanical ventilation, n33 (50.0)
      Length of mechanical ventilation, hrs90 [32.0 – 216.0]
      Inotropes/vasoactive drugs48 (76.2)
      Duration of inotropes/vasoactives, hrs57 [17.8 – 137.5]
      New-onset AKI, n (%)12 (19.0)
      Laboratory values
      Hemoglobin at admission, g/L137 [124.5 – 147]
      Leucocytes at admission, G/L12.6 [10.0 – 16.5]
      Lactate at implantation, mmol/L2.4 [1.6 – 4.4]
      Creatinine at implantation, μmol/L83 [70 – 103]
      Peak creatinine, μmol/L107 [89.5 – 154.5]
      Troponin T at admission, ng/L200 [48.5 – 1872]
      Peak troponin T, ng/L9820 [4082 – 18477.5]
      Peak creatine kinase, U/L5156 [2450.8 – 6853.5]
      ALT, U/L64 [30.5 – 158]
      ALT, alanine aminotransferase; AKI, acute kidney injury; IABP, intra-aortic balloon pump; ICU, intensive care unit; LAD, left anterior descending artery; LM, left main; LVEDP, left ventricular end-diastolic pressure; MAP, mean arterial pressure; MCS, mechanical circulatory support; PCI, percutaneous coronary intervention
      Table 3In-hospital outcomes.
      All patients (n=66)
      Outcomes
      Discharged to home, n (%)19 (28.8)
      Discharged to rehabilitation, n (%)26 (39.4)
      Discharged to nursing home, n (%)1 (1.5)
      Transferred to other hospital, n (%)4 (6.1)
      Died, n (%)16 (24.2)
      Causes of in-hospital death
      Cardiac causes, n (%)9 (13.6)
      Therapy withdrawal because of neurological prognosis, n (%)3 (4.5)
      Other, n (%)4 (6.1)
      We observed seven major vascular complications requiring vascular surgery and considerably high rate of major bleedings, which were mostly attributable to access related bleedings. Supplemental Table S3 lists all complications.
      The narratives of patients facing in-hospital death are shown in Supplemental Table S4. Therapy at hospital discharge is displayed in Supplemental Table S5.
      A total of five patients (8%) required implantation of a cardiac defibrillator during follow-up. Totally, 17 patients (26%) had died after six months follow-up. One patient received a LVAD after one month and one patient underwent heart transplantation two months after index presentation.

      Cardiac recovery by echocardiography

      Echocardiography at baseline was performed in the first days after hospital admission (median 1.0 [0.4 – 4.5] days). Overall, left ventricular ejection fraction (LVEF) was reduced (mean 34±12%), whereas left ventricular end-diastolic diameter, E/e’, and parameters of right ventricular dimension and function were within normal range.
      The echocardiographic follow-up was performed at median of 110 [77 – 163] days after Impella treatment. Follow-up echocardiography was unavailable in 3 patients, whereas 2 patients received LVAD or heart transplantation. Compared to baseline, LVEF at follow-up showed a significant increase to 48±13% (p<0.0001, Supplemental Figure S1), whereas LVEDD showed a statistically but not clinically significant increase from 49 mm [45 – 52] to 51 mm [47 – 55] (p=0.001, Supplemental Figure S2). The other echocardiographic parameters remained unchanged (Table 4, Supplemental Figure S3). Echocardiographic parameters of non-survivors are displayed in Supplemental Table S6.
      Table 4Echocardiographic parameters at baseline
      Median 0.95 days [0.4 – 4.5] after admission
      and at first follow-up
      Median 109.5 days [76.8 – 163.45] after device implantation
      .
      All patients (n=66)Survivors (n=50)First follow-upp-value
      Survivors at baseline compared to first follow-up.
      LVEF, %34±1236±1148±13<0.0001
      LVEDD, mm49 [45 – 52]48 [45.0 – 52.0]51 [47 – 55]0.001
      LVEDDi, mm/m225.6 ±4.025.5±4.126.5±3.30.001
      E/e’9.6 [8.0 – 11.9]9.6 [8.0 – 11.6]9.3 [6.9 – 12]0.32
      LAVi, ml/m228 [23 – 42]28 [23 – 43]29 [21 – 36]0.86
      TAPSE, mm22 [19 – 24]22 [19 – 24]22 [20 – 26]0.03
      RV S’, cm/s14.6±4.215.6±4.213.9±3.60.22
      TR Vmax, m/s2.8 [2.5 – 3.5]2.8 [2.4 – 2.8]2.4 [2.2 – 3.0]0.09
      RVEDAi, cm2/m29.4 [7.5 – 11.5]9.2 [7.0 – 10.5]8.5 [7.3 – 10.4]0.25
      LAVi, left atrial volume index; LVEDD, left ventricular diastolic diameter; LVEDDi, left ventricular diastolic diameter index; LVEF, left ventricular ejection fraction; RVEDAi, right ventricular end-diastolic area index; RV S’, right ventricular systolic excursion velocity; TAPSE, tricuspid annular plane systolic excursion; TR Vmax, tricuspid regurgitation peak jet velocity.
      Median 0.95 days [0.4 – 4.5] after admission
      Median 109.5 days [76.8 – 163.45] after device implantation
      Survivors at baseline compared to first follow-up.
      A total of 28 patients (62%) were identified as responders (i.e., ≥ 10% absolute increase of LVEF at follow-up), whereas 17 patients (38%) were non-responders (Figure 2). Of them, 13 (29%) showed a modest LVEF improvement (absolute increase between 0 and 9%) and 4 (9%) showed a LVEF worsening.
      Figure thumbnail gr2
      Figure 2Trajectory of left ventricular ejection fraction from baseline* to first follow-up., Green: patients with a ≥ 10% absolute increase of LVEF at follow-up., Red: patients without a ≥ 10% absolute increase of LVEF at follow-up., LVEF, left ventricular ejection fraction., * Median 0.95 days [0.4 – 4.5] after admission, Median 109.5 days [76.8 – 163.45] after device implantation
      Among the performed univariate analyses, low baseline creatinine was the only significant predictor of response (Table 5).
      Table 5Comparison of baseline characteristics in responders to non-responders
      Responders* (n=28)Non-responders (n=17)p-value
      Age, years62.8 ±10.662.8 ±9.00.98
      Male, n (%)24 (85.7)16 (94.1)0.63
      BMI, kg/m224.4 [23.2 -28.4]28 [24.4 – 28.7]0.22
      OHCA, n (%)13 (46.4)7 (41.2)0.76
      History of CAD, n (%)5 (17.9)6 (35.3)0.28
      GRACE score, points176 [162 – 198]178 [155 – 189]0.82
      Cardshock score, points3 [2 – 4]2 [1 – 3.5]0.41
      New onset AKI, n (%)4 (15.4)3 (17.6)>0.99
      Creatinine at baseline, μmol/L75 [57 – 86]86 [76.5 – 97.5]0.018
      HR at implantation, bpm92±3189±240.72
      LVEDP at implantation, mmHg33.4 ±8.731 ±11.30.54
      Lactate at implantation2 [1.4 – 3]1.9 [1.5 – 4.9]0.97
      Peak troponin T, ng/L7840 [4726 – 14547]9760 [2631 – 15480]0.99
      Impella before PCI, n (%)22 (78.6)11 (64.7)0.32
      Impella support duration, hrs32.3 [22.9 – 51.8]25.1 [23.6 – 49.7]0.87
      LM as culprit vessel, n (%)1 (3.6)2 (11.8)0.54
      LVEF at baseline, %32± 941±140.046
      LVEDDi at baseline, mm/m226.1±3.924.3±4.20.14
      TAPSE at baseline < 17 mm, n (%)4 (14.3)0 (0)0.28
      Three-pillars GDMT at discharge, n (%)16 (57.1)9 (52.9)>0.99
      Four-pillars GDMT at discharge, n (%)5 (17.9)3 (17.6)>0.99
      Loop diuretics at discharge, n (%)11 (39.3)8 (47.1)0.75
      ACEi, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers; ARNI, angiotensin receptor-neprilysin inhibitors; BMI, body mass index; CAD, coronary artery disease; GDMT, guideline-directed medical therapy; LM, left main; LVEDP, left ventricular end-diastolic pressure; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonists; OHCA, out-of-hospital cardiac arrest; PCI, percutaneous coronary intervention; SGLT2i, sodium-glucose cotransporter 2 inhibitors.
      Defined as LVEF improvement ≥ 10% at follow-up.
      Defined as ACEi/ARB/ARNI + beta-blockers + MRA
      Defined as ACEi/ARB/ARNI + beta-blockers + MRA + SGLT2i

      DISCUSSION

      Anterior STEMI is commonly complicated by hemodynamic deterioration and cardiogenic shock, which in turn carry a high mortality risk.
      • Stone P.H.
      • Raabe D.S.
      • Jaffe A.S.
      • et al.
      Prognostic significance of location and type of myocardial infarction: independent adverse outcome associated with anterior location.
      • Tiller C.
      • Holzknecht M.
      • Reindl M.
      • et al.
      Estimating the extent of myocardial damage in patients with STEMI using the DETERMINE score.
      • French B.A.
      • Kramer C.M.
      Mechanisms of postinfarct left ventricular remodeling.
      A major contributor to morbidity and mortality following an anterior STEMI is represented by adverse cardiac remodeling.
      • Bahit M.C.
      • Kochar A.
      • Granger C.B.
      Post-Myocardial Infarction Heart Failure.
      The use of the Impella device in selected anterior STEMI patients with shock presentation may improve short-term outcomes, but it remains uncertain if it has a beneficial long-term impact on cardiac remodeling.
      • Attinger-Toller A.
      • Bossard M.
      • Cioffi G.M.
      • et al.
      Ventricular Unloading Using the ImpellaTM Device in Cardiogenic Shock.
      In this context our analysis highlights the following points:
      • (i)
        At long-term echocardiographic follow-up after anterior STEMI treated with the Impella device, most patients who survived the index event showed an improvement of LV function and stable parameters of ventricular dilation, diastolic function, and right ventricular function and dimension. Of note, 62% showed a prognostically significant ≥10% absolute increase of LVEF;
      • (ii)
        Baseline creatinine was the only significant predictor of response at univariate analysis;
      • (iii)
        Compared to a median expected mortality of 50% at 6 months by means of GRACE-ACS Score,
        • Fox K.A.A.
        • Dabbous O.H.
        • Goldberg R.J.
        • et al.
        Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE).
        our cohort showed a mortality of 26% at 6 months.

      Anterior STEMI and left ventricular remodeling

      In the contemporary era, in which STEMI is treated with primary PCI and optimal pharmacotherapy, almost one-half of patients demonstrate LV post-infarct remodeling.
      • van der Bijl P.
      • Abou R.
      • Goedemans L.
      • et al.
      Left Ventricular Post-Infarct Remodeling.
      Since post-MI heart failure has been associated with increased mortality,
      • Chew D.S.
      • Heikki H.
      • Schmidt G.
      • et al.
      Change in Left Ventricular Ejection Fraction Following First Myocardial Infarction and Outcome.
      ,
      • St John Sutton M.
      • Pfeffer M.A.
      • Plappert T.
      • et al.
      Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril.
      ,
      • Møller J.E.
      • Hillis G.S.
      • Oh J.K.
      • Reeder G.S.
      • Gersh B.J.
      • Pellikka P.A.
      Wall motion score index and ejection fraction for risk stratification after acute myocardial infarction.
      preventive measures limiting infarct size and counteracting LV remodeling are paramount in these patients.
      With respect to infarct localization, anterior localization seems associated with a larger extent of microvascular obstruction and larger infarct size, which results in a higher incidence of heart failure and adverse events (e.g. arrhythmias, secondary mitral regurgitation).
      • Stone P.H.
      • Raabe D.S.
      • Jaffe A.S.
      • et al.
      Prognostic significance of location and type of myocardial infarction: independent adverse outcome associated with anterior location.
      • Tiller C.
      • Holzknecht M.
      • Reindl M.
      • et al.
      Estimating the extent of myocardial damage in patients with STEMI using the DETERMINE score.
      • French B.A.
      • Kramer C.M.
      Mechanisms of postinfarct left ventricular remodeling.
      As a result, we decided to analyze the impact of Impella in a selected cohort of patients with anterior localization only, excluding patients with non-anterior infarction.
      Guideline-based medical therapy (GDMT) for heart failure can mitigate adverse negative remodeling by reducing afterload, sympathetic drive, and fibrosis. Nevertheless, in our analysis, GDMT with or without sodium-glucose cotransporter 2 inhibitors was not a significant predictor of LVEF increase at univariate analysis, which is an expected result since the study was underpowered in sample size and follow-up length to anticipate this effect.
      If LV unloading sustainingly prevents adverse cardiac remodeling or furthermore enhances cardiac recovery in patients presenting with acute MI complicated by cardiogenic shock remains unclear and certainly needs to be determined in further studies. To put our results into perspectives, we summarized the data from earlier pivotal studies, which analyzed LV recovery following acute MI, highlighted in Supplemental Table S7. Whilst LVEF recovery is generally seen with timely revascularization and GDMT in most of those studies including acute MI patients, which were mostly not treated with MCS, one needs to consider that we analyzed a distinct and furthermore very sick cohort presenting with large anterior STEMI depending upon MCS. In our anterior STEMI cohort that required Impella device support, an increase in LVEF of ≥10% was noted in almost two thirds of all surviving patients.

      Left ventricular unloading for the prevention of heart failure

      It has been hypothesized that the Impella device may have beneficial effects, by counteracting the detrimental impact of high wall stress and microvascular dysfunction following an anterior STEMI.
      Reducing LV volume and LVEDP by mechanically unloading reduces myocardial oxygen demand, activates cardioprotective signaling cascades that mitigate myocardial damage after reperfusion, and may also promote myocardial recovery, which ultimately lead to a reduced infarct size.
      • Esposito M.L.
      • Zhang Y.
      • Qiao X.
      • et al.
      Left Ventricular Unloading Before Reperfusion Promotes Functional Recovery After Acute Myocardial Infarction.
      ,
      • Kapur N.K.
      • Paruchuri V.
      • Urbano-Morales J.A.
      • et al.
      Mechanically Unloading the Left Ventricle Before Coronary Reperfusion Reduces Left Ventricular Wall Stress and Myocardial Infarct Size.
      Furthermore, observational studies on cardiac MRI suggested that LV unloading prevented cardiac dysfunction by preserving the global radial and circumferential strain, and systolic and diastolic strain rates in the remote myocardium.
      • Fukamachi D.
      • Yamada A.
      • Ohgaku A.
      • et al.
      Protective effect of the Impella on the left ventricular function after acute broad anterior wall ST elevation myocardial infarctions with cardiogenic shock: cardiovascular magnetic resonance imaging strain analysis.
      As stated in the methods section, the timing of Impella insertion in our cohort followed mainly two approaches depending on case-by-case clinical decision. Nevertheless, first evidence on animal models and observational trials seem favoring Impella implantation before revascularization, which may maximize the potential benefit of LV unloading.
      • Esposito M.L.
      • Zhang Y.
      • Qiao X.
      • et al.
      Left Ventricular Unloading Before Reperfusion Promotes Functional Recovery After Acute Myocardial Infarction.
      • Kapur N.K.
      • Paruchuri V.
      • Urbano-Morales J.A.
      • et al.
      Mechanically Unloading the Left Ventricle Before Coronary Reperfusion Reduces Left Ventricular Wall Stress and Myocardial Infarct Size.
      • Saku K.
      • Kakino T.
      • Arimura T.
      • et al.
      Left Ventricular Mechanical Unloading by Total Support of Impella in Myocardial Infarction Reduces Infarct Size, Preserves Left Ventricular Function, and Prevents Subsequent Heart Failure in Dogs.
      ,
      • O’Neill W.W.
      • Grines C.
      • Schreiber T.
      • et al.
      Analysis of outcomes for 15,259 US patients with acute myocardial infarction cardiogenic shock (AMICS) supported with the Impella device.
      ,
      • Tehrani B.N.
      • Truesdell A.G.
      • Sherwood M.W.
      • et al.
      Standardized Team-Based Care for Cardiogenic Shock.
      After completion of a pilot feasibility study,
      • Kapur N.K.
      • Alkhouli M.A.
      • DeMartini T.J.
      • et al.
      Unloading the Left Ventricle Before Reperfusion in Patients With Anterior ST-Segment–Elevation Myocardial Infarction: A Pilot Study Using the Impella CP.
      the STEMI-DTU trial is now ongoing to assess safety and effectiveness of LV unloading with an Impella CP device for 30 minutes before PCI in patients with acute anterior STEMI (NCT03947619).
      Our study provides real-world insight on the hypothesis that LV unloading could potentially counteract the impact of negative remodeling post-infarct even in the long-term, irrespective of when LV unloading occurs, and facilitate subsequent LV recovery. Further studies are needed to better understand the mechanisms and utility of the Impella device in these processes.

      The role of right ventricular function

      Right ventricular (RV) dysfunction after myocardial infarction has a detrimental impact on prognosis.
      • Antoni M.L.
      • Scherptong R.W.C.
      • Atary J.Z.
      • et al.
      Prognostic Value of Right Ventricular Function in Patients After Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention.
      ,
      • Gorter T.M.
      • Lexis C.P.H.
      • Hummel Y.M.
      • et al.
      Right Ventricular Function After Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention (from the Glycometabolic Intervention as Adjunct to Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction III Trial).
      Anterior localization seems less commonly associated with RV failure compared to other MI localizations in concomitant cardiogenic shock.
      • Lala A.
      • Guo Y.
      • Xu J.
      • et al.
      Right Ventricular Dysfunction in Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Hemodynamic Analysis of the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) Trial and Registry.
      This is confirmed in our cohort. On average, parameters of RV dimension and function at baseline were in the normal range and only 4 patients had tricuspid annular plane systolic excursion <17 mm. Interestingly, those patients were all responders at follow-up. Anyways, the impact of RV failure on recovery and prognosis of cardiogenic shock patients receiving LV unloading with an Impella device is poorly described and warrants further investigation .

      Limitations

      Our findings must be interpreted in the context of the following limitations. First, this is an observational single-center study, which may limit its generalizability, as well as its results to association, not causation. Second, the analyzed echocardiograms were obtained in most cases as part of clinical routine assessment and according to our local protocol. Due to clinical circumstances and/or limited availability of echocardiography staff, we encountered some variability in the timing of baseline and follow-up echocardiograms. As a result, the number of responders could have been potentially underestimated due to a partial recovery before the first echocardiogram. Third, the limited number of patients in our cohort may have failed to gain a statistical significance in some endpoints. Fourth, the absence of a control cohort of patients with anterior STEMI not treated with Impella or implanted with other MCS devices limits inference about the impact of Impella alone compared to usual care on the endpoints. However, this is beyond the scope of our study. Moreover, selecting a control cohort that consisted of patients without any device support or implanted with other MCS would have introduced an uncontrolled bias, particularly as Impella implantation in patients who presented with anterior STEMI was made on a case-by-case basis by the treating invasive cardiologist.

      CONCLUSIONS

      The present study highlights a positive trend in cardiac remodelling and function during the follow-up period of patients with acute anterior STEMI who received Impella support on top of standard therapies including primary PCI. Eventually, the results from ongoing randomized trials are needed to determine whether hemodynamic support and LV unloading with Impella devices prevents adverse cardiac remodeling and the new onset of heart failure following acute anterior STEMI.

      Uncited reference

      • Thiele H.
      • Akin I.
      • Sandri M.
      • et al.
      PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock.
      .

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