Immediate inflammatory response to mechanical circulatory support in a porcine model of severe cardiogenic shock.

BACKGROUND: In selected cases of cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is combined with trans valvular micro axial flow pumps (ECMELLA). Observational studies indicate that ECMELLA may reduce mortality but exposing the patient to two advanced mechanical support devices may affect the early inflammatory response. We aimed to explore inflammatory biomarkers in a porcine cardiogenic shock model managed with V-A ECMO or ECMELLA. METHODS: Fourteen landrace pigs had acute myocardial infarction-induced cardiogenic shock with minimal arterial pulsatility by microsphere embolization and were afterwards managed 1:1 with either V-A ECMO or ECMELLA for 4 h. Serial blood samples were drawn hourly and analyzed for serum concentrations of interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha, and serum amyloid A (SAA). RESULTS: An increase in IL-6, IL-8, and SAA levels was observed during the experiment for both groups. At 2-4 h of support, IL-6 levels were higher in ECMELLA compared to V-A ECMO animals (difference: 1416 pg/ml, 1278 pg/ml, and 1030 pg/ml). SAA levels were higher in ECMELLA animals after 3 and 4 h of support (difference: 401 ng/ml and 524 ng/ml) and a significant treatment-by-time effect of ECMELLA on SAA was identified (p = 0.04). No statistical significant between-group differences were observed in carotid artery blood flow, urine output, and lactate levels. CONCLUSIONS: Left ventricular unloading with Impella during V-A ECMO resulted in a more extensive inflammatory reaction despite similar end-organ perfusion.

Haemodynamic implications of VA-ECMO vs. VA-ECMO plus Impella CP for cardiogenic shock in a large animal model.

AIMS: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with profound left ventricular (LV) failure is associated with inadequate LV emptying. To unload the LV, VA-ECMO can be combined with Impella CP (ECMELLA). We hypothesized that ECMELLA improves cardiac energetics compared with VA-ECMO in a porcine model of cardiogenic shock (CS). METHODS AND RESULTS: Land-race pigs (weight 70 kg) were instrumented, including a LV conductance catheter and a carotid artery Doppler flow probe. CS was induced with embolization in the left main coronary artery. CS was defined as reduction of ≥50% in cardiac output or mixed oxygen saturation (SvO2) or a SvO2 < 30%. At CS VA-ECMO was initiated and embolization was continued until arterial pulse pressure was <10 mmHg. At this point, Impella CP was placed in the ECMELLA arm. Support was maintained for 4 h. CS was induced in 15 pigs (VA-ECMO n = 7, ECMELLA n = 8). At time of CS MAP was <45 mmHg in both groups, with no difference at 4 h (VA-ECMO 64 mmHg ± 11 vs. ECMELLA 55 mmHg ± 21, P = 0.08). Carotid blood flow and arterial lactate increased from CS and was similar in VA-ECMO and ECMELLA [239 mL/min ± 97 vs. 213 mL/min ± 133 (P = 0.6) and 5.2 ± 3.3 vs. 4.2 ± 2.9 mmol/ (P = 0.5)]. Pressure-volume area (PVA) was significantly higher with VA-ECMO compared with ECMELLA (9567 ± 1733 vs. 6921 ± 5036 mmHg × mL/min × 10-3, P = 0.014). Total diureses was found to be lower in VA-ECMO compared with ECMELLA [248 mL (179-930) vs. 506 mL (418-2190); P = 0.005]. CONCLUSIONS: In a porcine model of CS, we found lower PVA, with the ECMELLA configuration compared with VA-ECMO, indicating better cardiac energetics without compromising systemic perfusion.

Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

Impact of Impella RP Versus Vasoactive Treatment on Right and Left Ventricular Strain in a Porcine Model of Acute Cardiogenic Shock Induced by Right Coronary Artery Embolization.

Background The response of the left ventricle to cardiogenic shock (CS) caused by right ventricular (RV) infarction and the effect of treatment with either vasoactive treatment or Impella RP are not well described. We sought to determine RV and left ventricular longitudinal strain (LS) by echocardiography after initiation of either Impella RP or vasoactive treatment for CS induced by right coronary artery embolization. Methods and Results CS was induced with microsphere embolization in the right coronary artery in 20 pigs. Shock was defined as a reduction in cardiac output of ≥50% and/or an SvO2 <30%. At the time of CS either Impella RP or vasoactive treatment (norepinephrine and milrinone) was initiated. Echocardiography and conductance measures were obtained at baseline, when CS was present, and 30, 90, and 180 minutes after induction of CS. Of 20 animals, 14 completed the protocol and were treated with either vasoactive treatment (n=7) or Impella RP (n=7); 6 animals died (3 in each group). In the RV there was a significantly higher LS with the vasoactive treatment compared with Impella RP (-7.6% [4.5] to -6.0% [5.2] vs -4.5% [6.6] to -14.2% [10.6]; P<0.006). Left ventricular LS improved with both treatments compared with shock, but with a larger effect (-9.4% [3.2] to -17.9% [3.6]) on LS with vasoactive treatment than Impella RP (-9.8% [3.1] to -12.3% [4.6]; P<0.001). We found a significant correlation between stroke work and RV LS (r=-0.60, P<0.001) and left ventricular LS (r=-0.62, P<0.001). Conclusions We found significantly higher hemodynamic effects with vasoactive treatment compared with Impella RP in both the RV and left ventricular but at a cost of increased stroke work.

Timing and Causes of Death in Acute Myocardial Infarction Complicated by Cardiogenic Shock (from the RETROSHOCK Cohort).

Acute myocardial infarction complicated by cardiogenic shock (AMICS) comprises a heterogeneous population with high mortality. Insight in timing and cause of death may improve understanding of the condition and aid individualization of treatment. This was assessed in a retrospective, multicenter observational cohort study based on 1,716 patients with AMICS treated during the period of 2010 to 2017, of whom 904 died before hospital discharge. Patients with AMICS were identified through national registries and review of individual patients charts. In 904 patients with AMICS who died before hospital discharge (median age 72 years [interquartile range (IQR) 63 to 79], 70% men), 342 (38%) had suffered out-of-hospital cardiac arrest. The most frequent cause of death was primary cardiac (54%), whereas 24% died of neurologic injury, and 20% of multiorgan failure (MOF). Time to death was 13 hours (IQR 5 to 43) for heart failure; 140 hours (IQR 95 to 209) in neurologic injury; and 137 hours (IQR 59 to 321) in MOF, p <0.001. The causes of death in patients presenting with out-of-hospital cardiac arrest (OHCA) were: neurologic injury in 57%, as opposed to 4% in patients not presenting with OHCA, p <0.001. In conclusion, in patients with AMICS, cause of death was mainly primary heart failure followed by neurologic injury and MOF. Median time from first medical contact to death was only 13 hours in patients dying from cardiac causes. The risk of dying of neurologic injury was low in patients without OHCA.

Biventricular Compared to Left Ventricular Impella and Norepinephrine Support in a Porcine Model of Severe Cardiogenic Shock.

Contemporary management of cardiogenic shock (CS) with vasopressors is associated with increased cardiac workload and despite the use of unloading devices such as the Impella pump, concomitant vasopressors are often necessary. Therefore, we compared if cardiac workload could be reduced and end-organ perfusion preserved with biventricular support (Bipella) compared to ImpellaCP and norepinephrine in pigs with left ventricular (LV) CS caused by left main coronary microembolization. Cardiac workload was calculated from heart rate × ventricular pressure-volume area obtained from conductance catheters placed in the LV and right ventricle (RV), whereas organ perfusion was measured from venous oxygen saturation in the pulmonary artery (SvO 2 ) and the kidney- and the cerebral vein. A cross-over design was used to access the difference after 30 minutes of ImpellaCP and norepinephrine 0.1 µg/kg/min versus Bipella for 60 minutes. Bipella treatment reduced LV workload ( p = 0.0078) without significant difference in RV workload from ImpellaCP and norepinephrine, however a decrease in SvO 2 (49[44-58] vs . 66[63-73]%, p = 0.01) and cerebral venous oxygen saturations (62[48-66] vs . 71[63-77]%, p = 0.016) was observed during Bipella compared to ImpellaCP and norepinephrine. We conclude that Bipella reduced LV workload but did not preserve end-organ perfusion compared to ImpellaCP and norepinephrine in short-term LV CS.

Impella RP Versus Pharmacologic Vasoactive Treatment in Profound Cardiogenic Shock due to Right Ventricular Failure.

The aim was to translationally compare a pharmacologic strategy versus treatment with the Impella RP in profound RV cardiogenic shock (CS). The pigs were allocated to either vasoactive therapy with norepinephrine (0.10 µg/kg/min) for the first 30 min, supplemented by an infusion of milrinone (0.4 µg/kg/min) for additional 150 min, or treatment with the Impella RP device for 180 min. Total RV workload (Pressure-volume-area × heart rate*103(mmHg/min)) remained unaffected upon treatment with the Impella RP and increased in the vasoactive group (CS 179[147;228] to norepinephrine 268[247;306](p = 0.002 compared to Impella RP) and norepinephrine + milrinone 366[329;422] (p = 0.002 compared to Impella RP). A trend towards higher venous cerebral oxygen saturation was observed with norepinephrine than Impella RP (Impella RP 51[47;61]% vs norepinephrine 62[57;71]%; p = 0.07), which became significantly higher with the addition of milrinone (Impella RP 45[32;63]% vs norepinephrine + milrinone 73[66;81]%; p = 0.002). The Impella RP unloaded the failing RV. In contrast, vasoactive treatment led to enhanced cerebral venous oxygen saturation.

Impact of concomitant vasoactive treatment and mechanical left ventricular unloading in a porcine model of profound cardiogenic shock.

BACKGROUND: Concomitant vasoactive drugs are often required to maintain adequate perfusion pressure in patients with acute myocardial infarction (AMI) and cardiogenic shock (CS) receiving hemodynamic support with an axial flow pump (Impella CP). OBJECTIVE: To compare the effect of equipotent dosages of epinephrine, dopamine, norepinephrine, and phenylephrine on cardiac work and end-organ perfusion in a porcine model of profound ischemic CS supported with an Impella CP. METHODS: CS was induced in 10 pigs by stepwise intracoronary injection of polyvinyl microspheres. Hemodynamic support with Impella CP was initiated followed by blinded crossover to vasoactive treatment with norepinephrine (0.10 µg/kg/min), epinephrine (0.10 µg/kg/min), or dopamine (10 µg/kg/min) for 30 min each. At the end of the study, phenylephrine (10 µg/kg/min) was administered for 20 min. The primary outcome was cardiac workload, a product of pressure-volume area (PVA) and heart rate (HR), measured using the conductance catheter technique. End-organ perfusion was assessed by measuring venous oxygen saturation from the pulmonary artery (SvO2), jugular bulb, and renal vein. Treatment effects were evaluated using multilevel mixed-effects linear regression. RESULTS: All catecholamines significantly increased LV stroke work and cardiac work, dopamine to the greatest extend by 341.8 × 103 (mmHg × mL)/min [95% CI (174.1, 509.5), p < 0.0001], and SvO2 significantly improved during all catecholamines. Phenylephrine, a vasoconstrictor, caused a significant increase in cardiac work by 437.8 × 103 (mmHg × mL)/min [95% CI (297.9, 577.6), p < 0.0001] due to increase in potential energy (p = 0.001), but no significant change in LV stroke work. Also, phenylephrine tended to decrease SvO2 (p = 0.063) and increased arterial lactate levels (p = 0.002). CONCLUSION: Catecholamines increased end-organ perfusion at the expense of increased cardiac work, most by dopamine. However, phenylephrine increased cardiac work with no increase in end-organ perfusion.

Prognostic importance of culprit lesion location in cardiogenic shock due to myocardial infarction.

BACKGROUND: As existing results are diverging, and the patient population has changed significantly, this study sought to investigate the prognostic importance of the culprit lesion location in patients with cardiogenic shock due to myocardial infarction (AMICS), in a contemporary and unselected patient population. METHODS: From the recruitment area of two tertiary heart centres in Denmark, covering 3.9 million citizens corresponding to two-thirds of the Danish population, all AMICS patients in the period of 2010-2017 were individually identified and validated through patient records. RESULTS: A total of 1716 patients with AMICS were identified. Immediate revascularization was performed in 1482 patients (86%). Among these, a culprit lesion in the left main coronary artery (LM) was associated with the highest 30-day mortality rate (66%), plogrank<0.0001, which persisted after multivariable adjustment for variables known to be associated with mortality in AMICS, including age, gender, heart rate, lactate, diabetes, stroke and out-of-hospital cardiac arrest, p=0.002. A culprit lesion in the remaining coronary arteries had comparable and lower 30-day mortality (43-48%), plogrank=0.39. Patients with multivessel disease had comparable prognoses irrespective of whether a culprit-only or multivessel percutaneous coronary intervention strategy was used (plogrank=0.80), and whether partial or complete revascularization was achieved (plogrank=0.24). CONCLUSIONS: Among AMICS patients undergoing revascularization, a LM culprit lesion was associated with the highest short-term mortality, whereas patients with a culprit lesion in the remaining coronary arteries had comparable and lower mortality rates. Multivessel disease patients had similar prognoses irrespective of percutaneous coronary intervention approach and whether partial or complete revascularization was achieved.

Temporal trends in incidence and patient characteristics in cardiogenic shock following acute myocardial infarction from 2010 to 2017: a Danish cohort study.

AIM: We sought to describe the contemporary annual incidence of cardiogenic shock (CS) following acute myocardial infarction (AMICS), the proportion of patients developing CS following ST-elevation myocardial infarction (STEMI), and other temporal changes in AMICS in Denmark between 2010 and 2017. METHODS AND RESULTS: Medical records of patients suspected of having AMICS during 2010-2017 were reviewed to identify consecutive patients with AMICS in a cohort corresponding to two-thirds of the Danish population. Due to changes in recruitment area over the study period, population-based incidence could only be calculated from 2012 to 2017. A total of 1716 patients with AMICS were identified and an increase in the annual incidence was observed, from a nadir 65.3 per million person-years in 2013 to 80.0 per million person-years in 2017 (P-value for trend < 0.001). This trend corresponded to an increase in patients with non-STEMI and a decrease in patients developing CS after STEMI (10.0-6.6%, P-value for trend < 0.001) Also, mean arterial blood pressure at the time of AMICS was lower (63 ± 11 mmHg to 61 ± 13 mmHg, P-value for trend = 0.001) and the frequency of patients with left ventricular ejection fraction ≤ 30% increased (61.8%-71.4%, P-value for trend = 0.004). The annual 30-day mortality during the study period remained unchanged at about 50%. CONCLUSION: The incidence rate of AMICS increased in the Danish population between 2012 and 2017. Fewer patients with STEMI developed CS, and haemodynamic severity of CS increased during the study period; however, survival rates remained unchanged.

Impella CP or VA-ECMO in profound cardiogenic shock: left ventricular unloading and organ perfusion in a large animal model.

AIMS: The aim of this study was to evaluate the Impella CP over veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and their impact on left ventricular unloading and end-organ perfusion. METHODS AND RESULTS: Cardiogenic shock (CS) was induced by injecting microspheres into the left coronary artery in fourteen adult female swine. Impella CP or VA-ECMO was initiated in the presence of CS and evaluated after 60 minutes. Left ventricular pressure-volume area (PVA, total mechanical work) was obtained from a conductance catheter. Results are presented as mean (95% confidence interval) and the rank-sum test was used to assess differences between devices. Compared to the CS state, PVA was unaffected by Impella CP and increased on VA-ECMO (from 2,548 [2,193; 2,904] mmHg x mL during CS to 5,775 [4,451; 7,099], between device p-value=0.02). Arterial lactate increased during CS and decreased on support with no difference between devices. Renal venous oxygen saturation decreased during CS and increased on support with no difference between devices. Cerebral venous oxygen saturation increased to 33% [25, 40] on Impella CP and to 69% [49, 89] on VA-ECMO, p=0.04. CONCLUSIONS: In this porcine model of profound CS, Impella CP unloaded the left ventricle compared to VA-ECMO. Both devices improved end-organ perfusion, with a tendency towards higher venous oxygen saturations on VA-ECMO.