Unloading the Left Ventricle Before Reperfusion in Patients With Anterior ST-Segment-Elevation Myocardial Infarction

Navin K. Kapur, Mohamad A. Alkhouli, Tony J. DeMartini, Haroon Faraz, Zachary H. George, Mark J. Goodwin, Jaime Hernandez-Montfort, Vijay S. Iyer, Noam Josephy, Sanjog Kalra, Amir Kaki, Richard H. Karas, Carey D. Kimmelstiel, Gerald C. Koenig, Evan Lau, Kapildeo Lotun, Ryan D. Madder, Salvatore F. Mannino, Perwaiz M. Meraj, Jason A. Moreland & 7 others Jeffrey W. Moses, Raymond L. Kim, Theodore L. Schreiber, James E. Udelson, Christian Witzke, David H.W. Wohns, William W. O'Neill

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

BACKGROUND: In ST-segment-elevation myocardial infarction (STEMI), infarct size correlates directly with heart failure and mortality. Preclinical testing has shown that, in comparison with reperfusion alone, mechanically unloading the left ventricle (LV) before reperfusion reduces infarct size and that 30 minutes of unloading activates a cardioprotective program that limits reperfusion injury. The DTU-STEMI pilot trial (Door-To-Unload in STEMI Pilot Trial) represents the first exploratory study testing whether LV unloading and delayed reperfusion in patients with STEMI without cardiogenic shock is safe and feasible. METHODS: In a multicenter, prospective, randomized exploratory safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events at 30 days. Efficacy parameters included the assessment of infarct size by using cardiac magnetic resonance imaging. RESULTS: All patients completed the U-IR (n=25) or U-DR (n=25) protocols with respective mean door-to-balloon times of 72 versus 97 minutes. Major adverse cardiovascular and cerebrovascular event rates were not statistically different between the U-IR versus U-DR groups (8% versus 12%, respectively, P=0.99). In comparison with the U-IR group, delaying reperfusion in the U-DR group did not affect 30-day mean infarct size measured as a percentage of LV mass (15±12% versus 13±11%, U-IR versus U-DR, P=0.53). CONCLUSIONS: We report that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is feasible within a relatively short time period in anterior STEMI. The DTU-STEMI pilot trial did not identify prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion. An appropriately powered pivotal trial comparing LV unloading before reperfusion to the current standard of care is required. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03000270.

Original languageEnglish (US)
Pages (from-to)337-346
Number of pages10
JournalCirculation
Volume139
Issue number3
DOIs
StatePublished - Jan 15 2019
Externally publishedYes

Fingerprint

Reperfusion
Heart Ventricles
Myocardial Infarction
Safety
ST Elevation Myocardial Infarction
Cardiogenic Shock
Standard of Care
Reperfusion Injury
Heart Failure
Magnetic Resonance Imaging
Clinical Trials
Equipment and Supplies
Mortality

Keywords

  • heart failure
  • heart ventricles
  • heart-assist devices
  • myocardial infarction
  • reperfusion injury

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Kapur, N. K., Alkhouli, M. A., DeMartini, T. J., Faraz, H., George, Z. H., Goodwin, M. J., ... O'Neill, W. W. (2019). Unloading the Left Ventricle Before Reperfusion in Patients With Anterior ST-Segment-Elevation Myocardial Infarction. Circulation, 139(3), 337-346. https://doi.org/10.1161/CIRCULATIONAHA.118.038269

Unloading the Left Ventricle Before Reperfusion in Patients With Anterior ST-Segment-Elevation Myocardial Infarction. / Kapur, Navin K.; Alkhouli, Mohamad A.; DeMartini, Tony J.; Faraz, Haroon; George, Zachary H.; Goodwin, Mark J.; Hernandez-Montfort, Jaime; Iyer, Vijay S.; Josephy, Noam; Kalra, Sanjog; Kaki, Amir; Karas, Richard H.; Kimmelstiel, Carey D.; Koenig, Gerald C.; Lau, Evan; Lotun, Kapildeo; Madder, Ryan D.; Mannino, Salvatore F.; Meraj, Perwaiz M.; Moreland, Jason A.; Moses, Jeffrey W.; Kim, Raymond L.; Schreiber, Theodore L.; Udelson, James E.; Witzke, Christian; Wohns, David H.W.; O'Neill, William W.

In: Circulation, Vol. 139, No. 3, 15.01.2019, p. 337-346.

Research output: Contribution to journalArticle

Kapur, NK, Alkhouli, MA, DeMartini, TJ, Faraz, H, George, ZH, Goodwin, MJ, Hernandez-Montfort, J, Iyer, VS, Josephy, N, Kalra, S, Kaki, A, Karas, RH, Kimmelstiel, CD, Koenig, GC, Lau, E, Lotun, K, Madder, RD, Mannino, SF, Meraj, PM, Moreland, JA, Moses, JW, Kim, RL, Schreiber, TL, Udelson, JE, Witzke, C, Wohns, DHW & O'Neill, WW 2019, 'Unloading the Left Ventricle Before Reperfusion in Patients With Anterior ST-Segment-Elevation Myocardial Infarction', Circulation, vol. 139, no. 3, pp. 337-346. https://doi.org/10.1161/CIRCULATIONAHA.118.038269
Kapur, Navin K. ; Alkhouli, Mohamad A. ; DeMartini, Tony J. ; Faraz, Haroon ; George, Zachary H. ; Goodwin, Mark J. ; Hernandez-Montfort, Jaime ; Iyer, Vijay S. ; Josephy, Noam ; Kalra, Sanjog ; Kaki, Amir ; Karas, Richard H. ; Kimmelstiel, Carey D. ; Koenig, Gerald C. ; Lau, Evan ; Lotun, Kapildeo ; Madder, Ryan D. ; Mannino, Salvatore F. ; Meraj, Perwaiz M. ; Moreland, Jason A. ; Moses, Jeffrey W. ; Kim, Raymond L. ; Schreiber, Theodore L. ; Udelson, James E. ; Witzke, Christian ; Wohns, David H.W. ; O'Neill, William W. / Unloading the Left Ventricle Before Reperfusion in Patients With Anterior ST-Segment-Elevation Myocardial Infarction. In: Circulation. 2019 ; Vol. 139, No. 3. pp. 337-346.
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TY - JOUR

T1 - Unloading the Left Ventricle Before Reperfusion in Patients With Anterior ST-Segment-Elevation Myocardial Infarction

AU - Kapur, Navin K.

AU - Alkhouli, Mohamad A.

AU - DeMartini, Tony J.

AU - Faraz, Haroon

AU - George, Zachary H.

AU - Goodwin, Mark J.

AU - Hernandez-Montfort, Jaime

AU - Iyer, Vijay S.

AU - Josephy, Noam

AU - Kalra, Sanjog

AU - Kaki, Amir

AU - Karas, Richard H.

AU - Kimmelstiel, Carey D.

AU - Koenig, Gerald C.

AU - Lau, Evan

AU - Lotun, Kapildeo

AU - Madder, Ryan D.

AU - Mannino, Salvatore F.

AU - Meraj, Perwaiz M.

AU - Moreland, Jason A.

AU - Moses, Jeffrey W.

AU - Kim, Raymond L.

AU - Schreiber, Theodore L.

AU - Udelson, James E.

AU - Witzke, Christian

AU - Wohns, David H.W.

AU - O'Neill, William W.

PY - 2019/1/15

Y1 - 2019/1/15

N2 - BACKGROUND: In ST-segment-elevation myocardial infarction (STEMI), infarct size correlates directly with heart failure and mortality. Preclinical testing has shown that, in comparison with reperfusion alone, mechanically unloading the left ventricle (LV) before reperfusion reduces infarct size and that 30 minutes of unloading activates a cardioprotective program that limits reperfusion injury. The DTU-STEMI pilot trial (Door-To-Unload in STEMI Pilot Trial) represents the first exploratory study testing whether LV unloading and delayed reperfusion in patients with STEMI without cardiogenic shock is safe and feasible. METHODS: In a multicenter, prospective, randomized exploratory safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events at 30 days. Efficacy parameters included the assessment of infarct size by using cardiac magnetic resonance imaging. RESULTS: All patients completed the U-IR (n=25) or U-DR (n=25) protocols with respective mean door-to-balloon times of 72 versus 97 minutes. Major adverse cardiovascular and cerebrovascular event rates were not statistically different between the U-IR versus U-DR groups (8% versus 12%, respectively, P=0.99). In comparison with the U-IR group, delaying reperfusion in the U-DR group did not affect 30-day mean infarct size measured as a percentage of LV mass (15±12% versus 13±11%, U-IR versus U-DR, P=0.53). CONCLUSIONS: We report that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is feasible within a relatively short time period in anterior STEMI. The DTU-STEMI pilot trial did not identify prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion. An appropriately powered pivotal trial comparing LV unloading before reperfusion to the current standard of care is required. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03000270.

AB - BACKGROUND: In ST-segment-elevation myocardial infarction (STEMI), infarct size correlates directly with heart failure and mortality. Preclinical testing has shown that, in comparison with reperfusion alone, mechanically unloading the left ventricle (LV) before reperfusion reduces infarct size and that 30 minutes of unloading activates a cardioprotective program that limits reperfusion injury. The DTU-STEMI pilot trial (Door-To-Unload in STEMI Pilot Trial) represents the first exploratory study testing whether LV unloading and delayed reperfusion in patients with STEMI without cardiogenic shock is safe and feasible. METHODS: In a multicenter, prospective, randomized exploratory safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events at 30 days. Efficacy parameters included the assessment of infarct size by using cardiac magnetic resonance imaging. RESULTS: All patients completed the U-IR (n=25) or U-DR (n=25) protocols with respective mean door-to-balloon times of 72 versus 97 minutes. Major adverse cardiovascular and cerebrovascular event rates were not statistically different between the U-IR versus U-DR groups (8% versus 12%, respectively, P=0.99). In comparison with the U-IR group, delaying reperfusion in the U-DR group did not affect 30-day mean infarct size measured as a percentage of LV mass (15±12% versus 13±11%, U-IR versus U-DR, P=0.53). CONCLUSIONS: We report that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is feasible within a relatively short time period in anterior STEMI. The DTU-STEMI pilot trial did not identify prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion. An appropriately powered pivotal trial comparing LV unloading before reperfusion to the current standard of care is required. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03000270.

KW - heart failure

KW - heart ventricles

KW - heart-assist devices

KW - myocardial infarction

KW - reperfusion injury

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