Door-to-unload: Left Ventricular Unloading Before Reperfusion in ST-elevation Myocardial Infarction

Figures & data

Table 1. Preclinical studies assessing left ventricle unloading with Impella prior to reperfusion.

Animal/device	Occluded vessel	Duration of ischemia (min)	Duration of reperfusion (min)	Study design	Infarct size end point	Infarct size (%)	Study (year)
Sheep (Impella 5.0)	LAD	60	120	Group 1: reperfusion only (control) Group 2: full support from onset of ischemia (60 min) and during reperfusion Group 3: full support during reperfusion Group 4: partial support during reperfusion	Infarct percent size (TTC and Evan’s blue)	Group 1: 67.2 ± 4.6% Group 2: 18.1 ± 10% Group 3: 41.6 ± 5.8% Group 4: 54.0 ± 8%	Meyns et al. (2003)
Swine (Impella CP^®)	LAD	90	120	Group 1: reperfusion only (control) Group 2: 60 min support before reperfusion	Infarct percent size (TTC)	Group 1: 74 ± 11% Group 2: 42 ± 8%	Kapur et al. (2015)
Swine (Impella)	LAD	90	120	Group 1: reperfusion only (control) Group 2: 15 min support before reperfusion Group 3: 30 min support before reperfusion Group 4: 60 min support before reperfusion Group 5: 30 min reperfusion followed by LV unloading and an additional 120 min reperfusion	Reduction in infarct size^† (TTC)	Group 1: no Group 2: no Group 3: yes Group 4: yes Group 5: no	Kapur et al. (2015)^†
Swine (Impella LD)	LCx	120	120	Group 1: reperfusion only (control) Group 2: support (90 min after onset of ischemia and during reperfusion)	Infarct percent size	Group 1: 35.3 ± 6.2% Group 2: 18.1 ± 4.8%	Sun et al. (2015)
Swine (Impella CP)	LAD	90	120	Group 1: reperfusion only (control) Group 2: 15 min support before reperfusion Group 3: 30 min support before reperfusion Group 4: 30 min reperfusion followed by 90 min reperfusion with support	Infarct percent size (TTC and Evan’s blue)	Group 1: 62.2 ± 1.7% Group 2: NS^‡ Group 3: 33.3 ± 5% Group 4: NS^‡	Esposito et al. (2018)
Canine (Impella CP)	LAD (+LCx)	180	60	Group 1: sham (thoracotomy only) Group 2: reperfusion only (control) Group 3: partial support (60 min after onset of ischemia to 60 min after reperfusion) Group 4: full support (60 min after onset of ischemia to 60 min after reperfusion)	Infarct percent size (TTC)	Group 1: NA Group 2: 16.3 ± 2.6% Group 3: 8.5 ± 4.3% Group 4: 2.1 ± 1.6%	Saku et al. (2018)
Swine (Impella CP)	LAD	120	180	Group 1: 30 min continued occlusion (control) Group 2: 30 min Impella support before reperfusion Group 3: 30 min extracorporeal membrane oxygenation support before reperfusion	Infarct percent size (TTC and Evan’s blue)	Group 1: 52 ± 15% Group 2: 34 ± 6% Group 3: NS	Briceno et al. (2019)
Swine (Impella CP)	LAD	60	120	Group 1: reperfusion only (control) Group 2: support only before reperfusion Group 3: support with immediate reperfusion	Infarct percent size (TTC and Evan’s blue)	Group 1: 54.7 ± 20.3% Group 2: 43.3 ± 24.6% Group 3: 22.1 ± 13.4%	Ko et al. (2020)

† This preclinical study was reported in a TCT presentation. An additional metric of infarct size reduction, infarct size as percentage of area at risk, was presented as a figure accompanying the presentation; however, exact measurements were not provided. Per the figure bar charts, infarct size as a percentage of area-at-risk was ∼67% in group 1, ∼60% in group 2, ∼30% in group 3, ∼40% in group 4 and ∼55% in group 5, indicating that best infarct size outcome was achieved with 30 min of unloading prior to reperfusion.

‡ Infarct percent sizes in group 2 and 4 were not provided; however, the authors state that unloading followed by perfusion in these two groups failed to reduce infarct size compared with reperfusion alone.

LAD: Left anterior descending; LCx: Left circumflex; LV: Left ventricle; NA: Not available; NS: No significant reduction; TTC: Triphenyltetrazolium chloride.

Table 2. Full inclusion and exclusion criteria for the STEMI-DTU pivotal trial.

Inclusion criteria
1. Age 18–80 years 2. First myocardial infarction 3. Acute anterior STEMI with ≥2 mm in two or more contiguous anterior leads or ≥4 mm total ST-segment deviation sum in the anterior leads v1–v4 4. Patient presents to the hospital between 1–5 h of chest pain onset 5. Patient indicated for Primary PCI 6. Patient or the patient’s legally authorized representative (where applicable) has signed informed consent
Exclusion criteria
1. Patient transferred from an outside hospital where invasive coronary procedure was attempted (including diagnostic catheterization) 2. Unwitnessed cardiac arrest or ≥30 min of cardiopulmonary resuscitation prior to enrollment or any impairment in mental status, cognition or any global or focal neurological deficit 3. Administration of fibrinolytic therapy within 24 h prior to enrollment 4. Cardiogenic shock defined as: systemic hypotension (systolic blood pressure <90 mmHg or the need for inotropes/pressors to maintain a systolic BP >90 mmHg) plus one of the following: any requirement for pressors/inotropes prior to arrival at the catheterization laboratory, clinical evidence of end organ hypoperfusion or use of intra-aortic balloon pump or any other circulatory support device 5. Inferior STEMI or suspected right ventricular failure 6. Any contraindication or inability to place the Impella, including peripheral vascular disease, tortuous vascular anatomy, femoral bruits or absent pedal pulses 7. Severe aortic stenosis 8. Acute cardiac mechanical complication: LV-free wall rupture OR interventricular septum rupture OR acute mitral regurgitation 9. Suspected or known pregnancy 10. Suspected systemic active infection 11. History or known hepatic insufficiency prior to catheterization 12. On renal replacement therapy 13. Chronic obstructive pulmonary disease with home oxygen therapy or on chronic steroid therapy 14. Known or evidence of prior myocardial infarction, including pathologic Q waves in nonanterior leads 15. Prior coronary artery bypass grafting or LAD PCI 16. History of heart failure 17. Prior aortic valve surgery or transcatheter aortic valve replacement 18. Left bundle branch block (new or old) 19. History of stroke/transient ischemic attack within the prior 3 months, any history of intracranial hemorrhage or any permanent neurological deficit 20. History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), any recent genitourinary or gastrointestinal bleed or will refuse blood transfusions 21. Patient on systemic anticoagulation preprocedure (including factor Xa inhibitors, thrombin inhibitors and warfarin) Known contraindication to: 22. Unable to undergo MRI or contraindication to use of gadolinium, e.g., CrCl <30 ml/min, noncompatible implant, claustrophobia 23. Contraindication to heparin, pork, pork products or contrast media 24. Contraindication to receiving a drug-eluting stent 25. Participation in the active treatment or follow-up phase of another clinical study of an investigational drug or device which has not reached its primary end point 26. Any organ condition, concomitant disease (e.g., psychiatric illness, severe alcoholism, or drug abuse, severe cancer, hepatic or kidney disease), with life expectancy of ≤2 years or other abnormality that itself, or the treatment of which, could interfere with the conduct of the study or that, in the opinion of the Investigator and/or sponsor’s medical monitor, would pose an unacceptable risk to the patient in the study 27. Subject has other medical, social or psychological problems that, in the opinion of the Investigator, compromises the subject’s ability to give written informed consent and/or to comply with study procedures including follow-up CMRs 28. Subject belongs to a vulnerable population (vulnerable patient populations are defined as Individuals with mental disability, persons in nursing homes, children, impoverished persons, homeless persons, nomads, refugees and those permanently incapable of giving informed consent. Vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the sponsor, members of the armed forces and persons kept in detention)

CMR: Cardiac magnetic resonance; LAD: Left anterior descending; LV: Left ventricle; PCI: Percutaneous coronary intervention; STEMI: ST-elevation myocardial infarction.

Figure 1. Protocol.

CMR: Cardiac magnetic resonance; LAR: Legal authorized representative; LV: Left ventricle; LVEDP: Left ventricle end diastolic pressure; PCI: Percutaneous coronary intervention.

Figure 2. Study end points.