Systems and methods for left ventricular unloading in treating myocardial infarction

Abstract

We provide herein a method of preventing or limiting the effects of heart failure in a human patient that has sustained myocardial infarction by reducing maladaptive cardiac remodeling in the patient. The method comprises percutaneously inserting a transvalvular blood pump, comprising a rotor and a cannula, into the patient's vasculature and positioning the cannula across the aortic valve of the patient's heart, with a distal end of the cannula located in the left ventricle of the heart and a proximal end of the pump located in the aorta. The method then comprises, prior to reperfusing the heart, operating the positioned pump to unload the left ventricle at a pumping rate of at least 2.5 L/min of blood flow for a support period between at least 30 minutes and less than 60 minutes. Then, after the support period, the method comprises applying coronary reperfusion therapy to the heart.

1 - 131 . (canceled) 
     
     
         132 . A method of supporting a human patient's heart that has sustained myocardial infarction, comprising the steps of:
 inserting a mechanical circulatory support device into the patient after the myocardial infarction, the mechanical circulatory support device comprising a cannula inserted into the heart across a valve;   prior to re-perfusing the heart, operating the mechanical circulatory support device for a support period between at least 30 minutes and less than 60 minutes, at a rate of at least 2.5 L/min of blood flow; and   after the support period, applying reperfusion therapy to the heart.   
     
     
         133 . The method of  claim 132 , wherein the mechanical circulatory support device is operated at a rate that provides a cardiac output of at least 3.5 L/min of blood flow. 
     
     
         134 . The method of  claim 132 , wherein the heart is unloaded by the mechanical circulatory support device concurrently with reperfusion. 
     
     
         135 . The method of  claim 132 , comprising the step of supporting the heart by an intra-aortic balloon pump or an extracorporeal membrane oxygenation (ECMO) pump, in combination with the mechanical circulatory support device. 
     
     
         136 . The method of  claim 132 , wherein reperfusion therapy comprises at least one of primary percutaneous coronary intervention (PCI) and fibrinolysis. 
     
     
         137 . The method of  claim 132 ,
 wherein the mechanical circulatory support device comprises a transvalvular blood pump, the blood pump percutaneously inserted into the patient and positioned across the aortic valve of the patient's heart, with a distal end of the pump located in the left ventricle of the heart, and   wherein prior to re-perfusing the heart, the positioned pump is operated to unload the left ventricle at a pumping rate of at least 2.5 L/min of blood flow for the support period of between at least 30 minutes and less than 60 minutes.   
     
     
         138 . The method of  claim 137 , comprising the step of:
 removing the blood pump from the patient's heart after applying the reperfusion therapy.   
     
     
         139 . The method of  claim 132 , wherein the mechanical circulatory support device is inserted percutaneously into the patient. 
     
     
         140 . The method of  claim 132 , comprising the steps of:
 reducing levels of BAX protein and active Caspase-3 antibody in patient cardiac tissue near the myocardial infarction; and   increasing levels of BCL-2 and BCL-XL proteins in patient cardiac tissue near the myocardial infarction.   
     
     
         141 . The method of  claim 132 , comprising the steps of:
 increasing stromal derived factor 1α (SDF-1α) protein levels in patient cardiac tissue near the myocardial infarction;   maintaining activity levels of MMP-2 and MMP-9 enzymes in patient cardiac tissue near the myocardial infarction; and   limiting upregulation of DPP-4 protein expression and activity in patient cardiac tissue near the myocardial infarction.   
     
     
         142 . The method of  claim 132 , comprising the steps of:
 reducing circulating levels of brain natriuretic peptide (BNP) in the patient's blood;   increasing mRNA levels of SERCA expression in patient cardiac cells near the myocardial infarction; and   reducing levels of calcineurin activity and Type I collagen in patient cardiac tissue near the myocardial infarction while maintaining levels of b-MHC in the non-infarct region of the patient's heart.   
     
     
         143 . The method of  claim 132 , wherein the heart has an ST Segment Elevation Sum (ΣSTE) of greater than 4, or greater than 5, or greater than 6. 
     
     
         144 . A method of preventing or limiting the effects of heart failure in a human patient that has sustained myocardial infarction by reducing maladaptive cardiac remodeling in the patient, the method comprising the steps of:
 percutaneously inserting a transvalvular blood pump, comprising a rotor and a cannula, into the patient's vasculature and positioning the cannula across the aortic valve of the patient's heart, with a distal end of the cannula located in the left ventricle of the heart and a proximal end of the pump located in the aorta;   prior to reperfusing the heart, operating the positioned pump to unload the left ventricle at a pumping rate of at least 2.5 L/min of blood flow for a support period between at least 30 minutes and less than 60 minutes; and   after the support period, applying coronary reperfusion therapy to the heart.   
     
     
         145 . The method of  claim 144 , wherein the pump is operated at a pumping rate of at least 3.5 L/min of blood flow. 
     
     
         146 . The method of  claim 144 , comprising the step of:
 continuing the operation of the pump in parallel with the application of coronary reperfusion.   
     
     
         147 . The method of  claim 144 , comprising the step of:
 continuing the operation of the pump in parallel with the application of coronary reperfusion for a total support period of at least 3 hours.   
     
     
         148 . The method of  claim 144 , comprising the step of:
 reducing at least one of: the infarct size and left ventricle scar size.   
     
     
         149 . The method of  claim 144 , comprising at least one of the steps of:
 reducing levels of BAX protein and active Caspase-3 antibody in patient cardiac tissue near the myocardial infarction;   increasing levels of BCL-2 and BCL-XL proteins in patient cardiac tissue near the myocardial infarction;   increasing stromal derived factor 1α (SDF-1α) protein levels in patient cardiac tissue near the myocardial infarction;   maintaining activity levels of MMP-2 and MMP-9 enzymes in patient cardiac tissue near the myocardial infarction;   limiting upregulation of DPP-4 protein expression and activity in patient cardiac tissue near the myocardial infarction;   reducing circulating levels of brain natriuretic peptide (BNP) in the patient's blood;   increasing mRNA levels of SERCA expression in patient cardiac cells near the myocardial infarction; and   reducing levels of calcineurin activity and Type I collagen in patient cardiac tissue near the myocardial infarction while maintaining levels of b-MHC in the non-infarct region of the patient's heart.   
     
     
         150 . The method of  claim 144 , wherein the heart has an ST Segment Elevation Sum (ΣSTE) of greater than 4. 
     
     
         151 . The method of  claim 144 , wherein reperfusion therapy comprises at least one of: primary percutaneous coronary intervention (PCI) and fibrinolysis. 
     
     
         152 . The method of  claim 151 , wherein PCI comprises implanting a stent in the patient. 
     
     
         153 . A method of preventing or limiting the effects of heart failure in a human patient that has sustained myocardial infarction by reducing maladaptive cardiac remodeling in the patient, the method comprising the steps of:
 increasing stromal derived factor 1α (SDF-1α) protein levels in patient cardiac tissue near the myocardial infarction;   maintaining activity levels of MMP-2 and MMP-9 enzymes in patient cardiac tissue near the myocardial infarction; and   limiting upregulation of DPP-4 protein expression and activity in patient cardiac tissue near the myocardial infarction.   
     
     
         154 . The method of  claim 153 , comprising the steps of:
 reducing levels of BAX protein and active Caspase-3 antibody in patient cardiac tissue near the myocardial infarction; and   increasing levels of BCL-2 and BCL-XL proteins in patient cardiac tissue near the myocardial infarction.   
     
     
         155 . The method of  claim 153 , comprising the steps of:
 reducing circulating levels of brain natriuretic peptide (BNP) in the patient's blood;   increasing mRNA levels of SERCA expression in patient cardiac cells near the myocardial infarction; and   reducing levels of calcineurin activity and Type I collagen in patient cardiac tissue near the myocardial infarction while maintaining levels of b-MHC in the non-infarct region of the patient's heart.   
     
     
         156 . The method of  claim 153 , wherein the heart has an ST Segment Elevation Sum (ΣSTE) of greater than 4, or greater than 5, or greater than 6. 
     
     
         157 . The method of  claim 153 , comprising the steps of:
 percutaneously inserting a transvalvular blood pump, comprising a rotor and a cannula, into the patient's vasculature and positioning the cannula across the aortic valve of the patient's heart, with a distal end of the cannula located in the left ventricle of the heart and a proximal end of the pump located in the aorta;   prior to reperfusing the heart, operating the positioned pump to unload the left ventricle at a pumping rate of at least 2.5 L/min of blood flow for a support period between at least 30 minutes and less than 60 minutes; and   after the support period, applying coronary reperfusion therapy to the heart.   
     
     
         158 . The method of  claim 157 , wherein the pump is operated at a pumping rate of at least 3.5 L/min of blood flow. 
     
     
         159 . The method of  claim 157 , wherein the heart is unloaded by the blood pump concurrently with reperfusion. 
     
     
         160 . The method of  claim 157 , comprising the step of supporting the heart by an intra-aortic balloon pump or an extracorporeal membrane oxygenation (ECMO) pump, in combination with the blood pump. 
     
     
         161 . The method of  claim 157 , wherein reperfusion therapy comprises at least one of primary percutaneous coronary intervention (PCI) and fibrinolysis. 
     
     
         162 . The method of  claim 157 , comprising the step of:
 removing the blood pump from the patient's heart after applying the reperfusion therapy.