Heart failure after an acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. We recently reported that activation of a transvalvular axial-flow pump in the left ...ventricle and delaying myocardial reperfusion, known as primary unloading, limits infarct size after AMI. The mechanisms underlying the cardioprotective benefit of primary unloading and whether the acute decrease in infarct size results in a durable reduction in LV scar and improves cardiac function remain unknown.
This study tested the importance of LV unloading before reperfusion, explored cardioprotective mechanisms, and determined the late-term impact of primary unloading on myocardial function.
Adult male swine were subjected to primary reperfusion or primary unloading after 90 min of percutaneous left anterior descending artery occlusion.
Compared with primary reperfusion, 30 min of LV unloading was necessary and sufficient before reperfusion to limit infarct size 28 days after AMI. Compared with primary reperfusion, primary unloading increased expression of genes associated with cellular respiration and mitochondrial integrity within the infarct zone. Primary unloading for 30 min further reduced activity levels of proteases known to degrade the cardioprotective cytokine, stromal-derived factor (SDF)-1α, thereby increasing SDF-1α signaling via reperfusion injury salvage kinases, which limits apoptosis within the infarct zone. Inhibiting SDF-1α activity attenuated the cardioprotective effect of primary unloading. Twenty-eight days after AMI, primary unloading reduced LV scar size, improved cardiac function, and limited expression of biomarkers associated with heart failure and maladaptive remodeling.
The authors report for the first time that first mechanically reducing LV work before coronary reperfusion with a transvalvular pump is necessary and sufficient to reduce infarct size and to activate a cardioprotective program that includes enhanced SDF-1α activity. Primary unloading further improved LV scar size and cardiac function 28 days after AMI.
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Highlights • Intra-aortic balloon pumps acutely reduce left ventricular stroke work by decreasing left ventricular systolic pressure not end-systolic volume. • Intra-aortic balloon pump activation ...increases the myocardial oxygen supply:demand ratio in advanced heart failure by decreasing systolic pressure and increasing diastolic pressure. • Intra-aortic balloon pumps may be more effective in patients with advanced heart failure who have low right heart filling pressures and high systemic vascular resistance.
Background Unloading the left ventricle and delaying reperfusion reduces infarct size in preclinical models of acute myocardial infarction. We hypothesized that a potential explanation for this ...effect is that left ventricular (LV) unloading before reperfusion increases collateral blood flow to ischemic myocardium. Methods and Results Acute myocardial infarction was induced by balloon occlusion of the left anterior descending artery for 120 minutes in adult swine, followed by reperfusion for 180 minutes. After 90 minutes of occlusion, animals were assigned to 30 minutes of continued occlusion (n=6) or to 30 minutes of support with either an Impella CP (n=4) or venoarterial extracorporeal membrane oxygenation (n=5) with persistent occlusion. The primary end point was measures of microcirculatory blood flow including the collateral flow index (CFI) during left anterior descending artery occlusion as (P
-RA)/(P
-RA), where P
, P
, and RA are aortic, coronary wedge, and right atrial pressure, respectively. Infarct size was quantified using triphenyltetrazolium chloride. Compared with continued occlusion, Impella, not venoarterial extracorporeal membrane oxygenation, reduced infarct size relative to the area at risk. Before reperfusion, Impella reduced LV stroke work by 25% and increased the CFI by 75%, but venoarterial extracorporeal membrane oxygenation did not. Among all groups, the change in CFI between 90 and 120 minutes correlated inversely with the change in LV stroke work (
=0.44,
=0.01) and infarct size (
=0.41,
=0.02). Conclusions We report for the first time that 30 minutes of LV unloading during coronary occlusion increases the CFI, which correlates inversely with LV stroke work and infarct size. Venoarterial extracorporeal membrane oxygenation failed to increase the CFI and did not reduce infarct size.
•This study represents the largest reported experience of Impella-supported myocarditis cases to date.•Patients treated with Impella for myocarditis in routine clinical practice have severe LV ...dysfunction and are in cardiogenic shock refractory to conventional therapy with the use of vasopressors, inotropes, and intra-aortic balloon pump.•Impella use appears to be safe in the settings of myocarditis complicated with cardiogenic shock.•Impella use can provide effective circulatory and ventricular support to allow for hemodynamic and myocardial recovery in patients with myocarditis complicated with cardiogenic shock.
Myocarditis complicated by cardiogenic shock remains a complex problem. The use of acute mechanical circulatory support devices for cardiogenic shock is growing. We explored the utility of Impella transvalvular microaxial flow catheters in the setting of myocarditis with cardiogenic shock.
We retrospectively analyzed data from 21 sites within the cVAD registry, an ongoing multicenter voluntary registry at sites in North America and Europe that have used Impella in patients with myocarditis. Myocarditis was defined by endomyocardial biopsy (n = 11) or by clinical history without angiographic evidence of coronary disease (n = 23). A total of 34 patients received an Impella 2.5, CP, 5.0, or RP device for cardiogenic shock complicating myocarditis. Baseline characteristics included age 42 ± 17 years, left ventricular ejection fraction (LVEF) 18% ± 10%, cardiac index 1.82 ± 0.46 L·min−1·m−2, pulmonary capillary wedge pressure 25 ± 7 mm Hg, and lactate 27 ± 31 mg/dL. Before Impella placement, 32% (n = 11) of patients required intra-aortic balloon pump. Mean duration of Impella support was 91 ± 74 hours; 21 of 34 patients (62%) survived the index hospitalization and were discharged with an improved mean LVEF of 37.32% ± 20.31% (P = .001); 15 patients recovered with successful support, 5 patients were transferred to another hospital on initial Impella support, 1 patient underwent orthotopic heart transplantation. Ten patients required transition to another mechanical circulatory support device.
This is the largest analysis of Impella-supported myocarditis cases to date. The use of Impella appears to be safe and effective in the settings of myocarditis complicated by cardiogenic shock.
Key Points
Rising urine NGAL and serum creatinine after 48 hr are potentially useful in predicting persistent creatinine increase in patients with contrast‐induced AKI.
Urinary NGAL may allow for ...early identification of a high‐risk cohort following PCI.
Future studies are needed to determine whether renal biomarkers are affected by clinical variables, such as heart failure acute mechanical circulatory support (AMCS) and whether they can be used to identify patients who would benefit from either AMCS reno‐protection during PCI remains unknown.
Hemolysis is a potential limitation of percutaneously delivered left‐sided mechanical circulatory support pumps, including trans valvular micro‐axial flow pumps (TVP). Hemolytic biomarkers among ...durable left ventricular assist devices include lactate dehydrogenase (LDH) >2.5 times the upper limit of normal (ULN) and plasma‐free hemoglobin (pf‐Hb) >20 mg/dL. We examined the predictive value of these markers among patients with cardiogenic shock (CS) receiving a TVP. We retrospectively studied records of 116 consecutive patients receiving an Impella TVP at our institution between 2012 and 2017 for CS. Twenty‐three met inclusion/exclusion criteria, and had sufficient pf‐Hb data for analysis. Area under receiver‐operator characteristic (ROC) curve for diagnosing hemolysis were calculated. Mean age was 62 ± 14 years and ejection fraction was 15 ± 5%. Mean duration of support was 5.4 ± 3.5 days. Pre‐device LDH levels were >2.5x ULN in 71% (n = 5/7) of 5.0 and 29% of CP patients, while pre‐device pf‐Hb levels were >20 mg/dL in 14% (n = 1/7) of 5.0 and 25% (n = 4/16) of CP patients. Given elevated baseline LDH and pf‐Hb levels, we defined hemolysis as a pf‐Hb level >40 mg/dL within 72 h post‐implant plus clinical evidence of device‐related hemolysis. We identified that 30% (n = 7/23) had device‐related hemolysis. Using ROC curve‐derived cut‐points, an increase in delta pf‐Hb by >27mg/dL, not delta LDH, within 24 h after TVP implant (delta pf‐Hb: C‐statistic = 0.79, sensitivity: 57%, specificity: 93%, p <0.05) was highly predictive of hemolysis. In conclusion, we identified a change in pf‐Hb, not LDH, levels is highly sensitive and specific for hemolysis in patients treated with a TVP for CS.
Acute heart failure refractory to medical therapy is a major cause of morbidity and mortality. The Aortix device (Procyrion Inc) is a percutaneously delivered entrainment pump positioned in the ...descending aorta.
Using the newest generation Aortix device in 8 adult male Yorkshire swine, we tested the hypothesis that positioning in the abdominal aorta may provide superior hemodynamic effects than thoracic positioning in a swine model of postinfarct left ventricular injury.Abdominal activation generated significantly larger transaortic gradients (proximal minus distal mean aortic pressures) than thoracic positioning at all pump speeds. Compared with baseline values, activation in the abdominal, not thoracic, position significantly increased cardiac output, reduced arterial elastance, and systemic vascular resistance at low speeds. Compared with baseline values, abdominal activation also increased transpulmonary pressure gradients at medium and high speed, which was driven by trends toward higher mean pulmonary artery pressure and lower pulmonary capillary wedge pressure.
This is the first report to determine that in contrast to thoracic positioning, abdominal positioning of the newest generation Aortix device reduces left ventricular afterload and increases cardiac output at low speeds. These findings have potentially important implications for the design of early clinical studies by suggesting that device position and speed are major determinants of improved hemodynamic efficacy.
New mechanistic insight into how the kidney responds to cardiac injury during acute myocardial infarction (AMI) is required. We hypothesized that AMI promotes inflammation and matrix ...metalloproteinase-9 (MMP9) activity in the kidney and studied the effect of initiating an Impella CP or veno-arterial extracorporeal membrane oxygenation (VA-ECMO) before coronary reperfusion during AMI. Adult male swine were subjected to coronary occlusion and either reperfusion (ischemia-reperfusion; IR) or support with either Impella or VA-ECMO before reperfusion. IR and ECMO increased while Impella reduced levels of MMP-9 in the myocardial infarct zone, circulation, and renal cortex. Compared to IR, Impella reduced myocardial infarct size and urinary KIM-1 levels, but VA-ECMO did not. IR and VA-ECMO increased pro-fibrogenic signaling via transforming growth factor-beta and endoglin in the renal cortex, but Impella did not. These findings identify that AMI increases inflammatory activity in the kidney, which may be attenuated by Impella support.
Mechanical Unloading in Heart Failure Uriel, Nir; Sayer, Gabriel; Annamalai, Shiva ...
Journal of the American College of Cardiology,
07/2018, Letnik:
72, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Myocardial injury induces significant changes in ventricular structure and function at both the cellular and anatomic level, leading to ventricular remodeling and subsequent heart failure. Unloading ...left ventricular pressure has been studied in both the short-term and long-term settings, as a means of preventing or reversing cardiac remodeling. In acute myocardial infarction, cardiac unloading is used to reduce oxygen demand and limit infarct size. Research has demonstrated the benefits of short-term unloading with mechanical circulatory support devices before reperfusion in the context of acute myocardial infarction with cardiogenic shock, and a confirmatory trial is ongoing. In chronic heart failure, ventricular unloading using mechanical circulatory support can reverse many of the cellular and anatomic changes that accompany ventricular remodeling. Ongoing research is evaluating the ability of left ventricular assist devices to promote myocardial recovery and remission from clinical heart failure.
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