Association between speckle tracking echocardiography and pressure-volume loops during cardiogenic shock development.

BACKGROUND: The relationship between speckle tracking assessed global longitudinal strain (GLS) and Doppler-based echocardiography with basic physiological markers of cardiac function derived from pressure-volume loops is poorly elucidated. OBJECTIVE: We aimed to describe the association between LS and Doppler-based echocardiography and direct measurements of central haemodynamic parameters from conductance catheter-based pressure-volume loops in an animal model with increasing left ventricular (LV) dysfunction. METHODS: 12 Danish landrace female pigs (75-80 kg) were used. All instrumentations were performed percutaneously, including the conductance catheter in the LV. Progressive LV dysfunction was induced by embolisation through the left main coronary artery with microspheres every 3 min until a >50% reduction in cardiac output (CO) or mixed venous saturation (SvO2), compared with baseline, or SvO2 <30%. Echocardiography was performed at baseline and 90 s after each injection. RESULTS: With progressive LV dysfunction, mean CO decreased from 5.6±0.9 L/min to 2.1±0.9 L/min, and mean SvO2 deteriorated from 61.1±7.9% to 35.3±6.1%. Mean LS and LV outflow tract velocity time integral (LVOT VTI) declined from -13.8±3.0% to -6.1±2.0% and 16.9±2.6 cm to 7.8±1.8 cm, respectively. LS and LVOT VTI showed the strongest correlation to stroke work in unadjusted linear regression (r2=0.53 and r2=0.49, respectively). LS correlated significantly with stroke volume, end-systolic elastance, systolic blood pressure, ventriculo-arterial coupling and arterial elastance. CONCLUSION: In an animal model of acute progressive LV dysfunction, echocardiographic and conductance catheter-based measurements changed significantly. LS and LVOT VTI displayed the earliest and the largest alterations with increased myocardial damage and both correlated strongest with stroke work.

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.

Circulating biomarkers of the CS4P and CLIP scores are not altered in a pig model of acute cardiogenic shock and additional short-term circulatory support.

BACKGROUND: Cardiogenic shock (CS) is the leading cause of death in patients with myocardial infarction with a mortality rate greater than 50%. Recently, the CS 4 Proteins (CS4P) and CLIP scores have been developed to predict survival in CS patients. However, their impact in acute CS and additional short-term left ventricular (LV) circulatory support as prognostic markers is currently not known. METHODS AND RESULTS: CS was induced in a porcine model by injecting microsphere particles into the left main coronary artery. Mechanical circulatory support was performed by additional percutaneous LV unloading using an Impella microaxial flow-pump for 30 minutes. Serum samples were collected at baseline, following the onset of CS, and additional LV unloading. Serum levels of biomarkers of the CS4P (beta-2-microglobulin, ALDOB, L-FABP, SerpinG1) and the CLIP scores (Cystatin C, Lactate, Interleukin-6, NT-proBNP) were neither different at any time point investigated nor did they correlate with cardiac output. CONCLUSION: The CS4P and CLIP scores do not reflect immediate whole-body dysregulation in acute CS and have not been able to predict the potential reversal following additional short-term mechanical support by LV unloading in our experimental model. The impact of both scores as prognostic markers after the immediate onset of CS and following additional short-term LV unloading to identify patients at greatest risk remains to be determined.

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.

Soluble ST2 in plasma is associated with post-procedural no-or-slow reflow after primary percutaneous coronary intervention in ST-elevation myocardial infarction.

AIM: The no-or-slow-reflow phenomenon after primary percutaneous coronary intervention is associated with more extensive myocardial injury in patients with ST-elevation myocardial infarction (STEMI). Soluble suppression of tumourigenicity 2 (sST2) is released in acute myocardial response to injury, and an increase in plasma level in the initial phase of STEMI is associated with increased mortality and risk of heart failure. We have therefore explored the association of pre-intervention plasma sST2 with the post-procedural no-or-slow-reflow phenomenon in patients with STEMI. METHODS AND RESULTS: We included consecutive patients with verified STEMI from two tertiary heart centres. Blood samples were collected at admission before angiography. Post-procedural coronary flow was assessed according to thrombolysis in myocardial infarction (TIMI) classification for STEMI. Patients were divided into two groups: post-procedural TIMI 0-2 as no-or-slow reflow and TIMI 3 as normal reflow. The association between sST2 and TIMI flow was explored using multiple logistic regression. A total of 1607 patients with available TIMI flow classification were included in the analysis. Normal reflow was seen in 1520 (94.6%), while 87 (5.4%) had no-or-slow reflow. No-or-slow-reflow patients had higher all-cause 30-day mortality [10 (11%) vs. 65 (4.3%), P = 0.006]. Pre-procedural sST2 was higher in the no-or-slow-flow group [47 ng/mL, interquartile range (IQR, 33-83) vs. 39 ng/mL (IQR 29-55), P < 0.001] and was independently associated with post-procedural no-or-slow flow [two-fold sST2 increase: odds ratio 1.44 (1.15-1.78), P = 0.0012]. CONCLUSION: In patients with STEMI, the sST2 level at admission before coronary angiography is independently associated with the post-procedural no-or-slow-reflow phenomenon.

miRNA-200b-A Potential Biomarker Identified in a Porcine Model of Cardiogenic Shock and Mechanical Unloading.

Background: Cardiogenic shock (CS) alters whole body metabolism and circulating biomarkers serve as prognostic markers in CS patients. Percutaneous ventricular assist devices (pVADs) unload the left ventricle by actively ejecting blood into the aorta. The goal of the present study was to identify alterations in circulating metabolites and transcripts in a large animal model that might serve as potential prognostic biomarkers in acute CS and additional left ventricular unloading by Impella ® pVAD support. Methods: CS was induced in a preclinical large animal model by injecting microspheres into the left coronary artery system in six pigs. After the induction of CS, mechanical pVAD support was implemented for 30 min total. Serum samples were collected under basal conditions, after the onset of CS, and following additional pVAD unloading. Circulating metabolites were determined by metabolomic analysis, circulating RNA entities by RNA sequencing. Results: CS and additional pVAD support alter the abundance of circulating metabolites involved in Aminoacyl-tRNA biosynthesis and amino acid metabolism. RNA sequencing revealed decreased abundance of the hypoxia sensitive miRNA-200b following the induction of CS, which was reversed following pVAD support. Conclusion: The hypoxamir miRNA-200b is a potential circulating marker that is repressed in CS and is restored following pVAD support. The early transcriptional response with increased miRNA-200b expression following only 30 min of pVAD support suggests that mechanical unloading alters whole body metabolism. Future studies are required to delineate the impact of serum miRNA-200b levels as a prognostic marker in patients with acute CS and pVAD unloading.

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.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) Measured at Admission is Associated With Development of Late Cardiogenic Shock and Mortality in Patients With ST-Segment Elevation Myocardial Infarction.

ABSTRACT: In patients with ST-elevation myocardial infarction (STEMI) the immune system is activated with an inflammatory response to follow. In STEMI patients with a severe inflammatory response, risk of development of cardiogenic shock (CS) seems increased. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a glycoprotein released from mature neutrophils and plasma concentration may increase immediately after STEMI. We therefore aimed to assess whether admission NGAL plasma concentration in patients with STEMI was associated with CS development after leaving the catheterization laboratory (late CS) and 30-day all-cause mortality. PATIENTS AND METHODS: From 1,892 consecutive patients with STEMI 1,626 (86%) had plasma NGAL concentration measured upon hospital admission before angiography throughout a 1-year period at two tertiary heart centers in Denmark. Patients were stratified according to NGAL quartiles (Q1-4). To assess late CS development, we adjusted for the Observatoire Régional Breton sur l'Infarctus risk score for late CS. For mortality assessment, we adjusted for gender, age, post-PCI culprit Thrombolysis in myocardial infarction flow, left ventricular ejection fraction (LVEF), kidney dysfunction, and being comatose after cardiac arrest. RESULTS: Increasing NGAL concentration was associated with higher age, more comorbidities, and more critical patient conditions including lower blood pressure and LVEF. When adjusted for factors associated with poor outcome, NGAL remained independently associated with both late CS development (Q4 vs. Q1-3) (OR (95% CI) 3.64 (1.79-7.41) and 30-day mortality (HR (95% CI) 3.18 (1.73-5.84)). CONCLUSION: Admission plasma concentration of NGAL in STEMI patients is independently associated with 30-day all-cause mortality and predictive of late CS development.

Phenotyping Cardiogenic Shock.

Background Cardiogenic shock (CS) is a heterogeneous syndrome with varied presentations and outcomes. We used a machine learning approach to test the hypothesis that patients with CS have distinct phenotypes at presentation, which are associated with unique clinical profiles and in-hospital mortality. Methods and Results We analyzed data from 1959 patients with CS from 2 international cohorts: CSWG (Cardiogenic Shock Working Group Registry) (myocardial infarction [CSWG-MI; n=410] and acute-on-chronic heart failure [CSWG-HF; n=480]) and the DRR (Danish Retroshock MI Registry) (n=1069). Clusters of patients with CS were identified in CSWG-MI using the consensus k means algorithm and subsequently validated in CSWG-HF and DRR. Patients in each phenotype were further categorized by their Society of Cardiovascular Angiography and Interventions staging. The machine learning algorithms revealed 3 distinct clusters in CS: "non-congested (I)", "cardiorenal (II)," and "cardiometabolic (III)" shock. Among the 3 cohorts (CSWG-MI versus DDR versus CSWG-HF), in-hospital mortality was 21% versus 28% versus 10%, 45% versus 40% versus 32%, and 55% versus 56% versus 52% for clusters I, II, and III, respectively. The "cardiometabolic shock" cluster had the highest risk of developing stage D or E shock as well as in-hospital mortality among the phenotypes, regardless of cause. Despite baseline differences, each cluster showed reproducible demographic, metabolic, and hemodynamic profiles across the 3 cohorts. Conclusions Using machine learning, we identified and validated 3 distinct CS phenotypes, with specific and reproducible associations with mortality. These phenotypes may allow for targeted patient enrollment in clinical trials and foster development of tailored treatment strategies in subsets of patients with CS.

Data-driven point-of-care risk model in patients with acute myocardial infarction and cardiogenic shock.

BACKGROUND: Prognosis models based on stepwise regression methods show modest performance in patients with cardiogenic shock (CS). Automated variable selection allows data-driven risk evaluation by recognizing distinct patterns in data. We sought to evaluate an automated variable selection method (least absolute shrinkage and selection operator, LASSO) for predicting 30-day mortality in patients with acute myocardial infarction and CS (AMICS) receiving acute percutaneous coronary intervention (PCI) compared to two established scores. METHODS AND RESULTS: Consecutive patients with AMICS receiving acute PCI at one of two tertiary heart centres in Denmark 2010-2017. Patients were divided according to treatment with mechanical circulatory support (MCS); PCI-MCS cohort (n = 220) versus PCI cohort (n = 1180). The latter was divided into a development (2010-2014) and a temporal validation cohort (2015-2017). Cohort-specific LASSO models were based on data obtained before PCI. LASSO models outperformed IABP-SHOCK II and CardShock risk scores in discriminative ability for 30-day mortality in the PCI validation [receiver operating characteristics area under the curve (ROC AUC) 0.80 (95% CI 0.76-0.84) vs 0.73 (95% CI 0.69-0.77) and 0.70 (95% CI 0.65-0.75), respectively, P < 0.01 for both] and PCI-MCS development cohort [ROC AUC 0.77 (95% CI 0.70-0.83) vs 0.64 (95% CI 0.57-0.71) and 0.64 (95% CI 0.57-0.71), respectively, P < 0.01 for both]. Variable influence differed depending on MCS, with age being the most influential factor in the LASSO-PCI model, whereas haematocrit and estimated glomerular filtration rate were the highest-ranking factors in the LASSO-PCI-MCS model. CONCLUSION: Data-driven prognosis models outperformed established risk scores in patients with AMICS receiving acute PCI and exhibited good discriminative abilities. Observations indicate a potential use of machinelearning to facilitate individualized patient care and targeted interventions in the future.

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.

Incidence, Predictors, and Outcome of In-Hospital Bleeding in Patients With Cardiogenic Shock Complicating Acute Myocardial Infarction.

Bleeding after acute myocardial infarction (AMI) is associated with an increased morbidity and mortality. The frequency and consequences of bleeding events in patients with AMICS are not well described. The objective was to investigate incidence and outcome of bleeding complications among unselected patients with AMI complicated by cardiogenic shock (AMICS) and referred for immediate revascularization. Bleeding events were assessed by review of medical records in consecutive AMICS patients admitted between 2010 and 2017. Bleedings during admission were classified according to Bleeding Academic Research Consortium classification. Patients who did not survive to admission in the intensive care unit were excluded. Of the 1,716 patients admitted with AMICS, 1,532 patients (89%) survived to ICU admission. At 30 days, mortality was 48%. Severe bleedings classified as BARC 3/5 were seen in 87 non-coronary bypass grafting patients (6.1%). Co-morbidity did not differ among patients; however, patients who had a BARC 3/5 bleeding had significantly higher lactate and lower systolic blood pressure at admission, indicating a more severe state of shock. The use of mechanical assist devices was significantly associated with severe bleeding events. Univariable analysis showed that patients with a BARC 3/5 bleeding had a significantly higher 30-day mortality hazard compared with patients without severe bleedings. The association did not sustain after multivariable adjustment (hazard ratio 0.90, 95% confidence interval 0.64; 1.26, p = 0.52). In conclusion, severe bleeding events according to BARC classification in an all-comer population of patients with AMICS were not associated with higher mortality when adjusting for immediate management, hemodynamic, and metabolic state. This indicates that mortality in these patients is primarily related to other factors.

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.

Proteomic Discovery and Validation of the Confounding Effect of Heparin Administration on the Analysis of Candidate Cardiovascular Biomarkers.

BACKGROUND: Several plasma proteins have been suggested as markers for a variety of cardiovascular conditions but fail to qualify in independent patient cohorts. This may relate to interference of medication on plasma protein concentrations. We used proteomics to identify plasma proteins that changed in concentration with heparin administration and therefore potentially may confound their evaluation as biomarkers in situations in which heparin is used. METHODS: We used a proteomic approach based on isobaric tagging and nano-LC-MS/MS analysis to quantify several hundred proteins in a discovery study in which individual plasma samples from 9 patients at intravascular ultrasound follow-up 12 months after an acute myocardial infarction before heparin administration and 2, 15, and 60 min after heparin administration; we validated our findings in 500 individual plasma samples obtained at admission from patients with suspected ST segment elevation myocardial infarction (STEMI), of whom 363 were treated with heparin before admission. RESULTS: In the discovery study, 25 of 653 identified plasma proteins displayed a changed concentration after heparin administration (Bonferroni-corrected P value at P < 7.66 × 10-5). Fourteen of the proteins changed significantly among heparin-treated patients in the validation study (nominal significance level of P < 6.92 × 10-5). Among heparin-affected proteins in both the discovery study and the validation study were midkine, spondin 1, secreted frizzled-like protein 1, lipoprotein lipase, and follistatin, all previously associated with STEMI. CONCLUSIONS: Medications such as heparin administration given before blood sampling may confound biomarker discovery and should be carefully considered in such studies.

Large Porcine Model of Profound Acute Ischemic Cardiogenic Shock.

Cardiogenic shock is one of the leading causes of death following acute myocardial infarction affecting 10% of patients with large myocardial infarcts with a subsequent mortality rate of 50%. Here we describe a large porcine model of acute ischemic cardiogenic shock. Acute left or right ventricular failure can be achieved with close to a 100% success rate by stepwise injection of microspheres into the left or right coronary artery, respectively, and the method allows for titration of heart failure to a prespecified level.

Support with intra-aortic balloon pump vs. Impella2.5® and blood flow to the heart, brain and kidneys - an experimental porcine model of ischaemic heart failure.

BACKGROUND: Cardiogenic shock as a complication to an acute myocardial infarction has an unacceptably high death rate that has not changed for the last 15years. Mortality is partly related to organ hypoperfusion and mechanical assist devices are used for the most severe cases but we do not know which assist device is the best option. Therefore, we have investigated how an IABP and an Impella®-pump influenced blood flow to the brain, heart and kidneys, in a closed-chest porcine model of severe left ventricular failure. METHODS: 13 pigs were anesthetised and left ventricular failure was induced by occluding the proximal LAD for 45min followed by 30min of reperfusion. Blood flow was measured in the carotid artery, the LAD, and the renal artery. The Impella® and IABP were inserted via the femoral arteries, and the two devices were tested individually and combined after induction of heart failure. RESULTS: Carotid- (p=0.01) and renal blood flow (p=0.045) were higher on Impella®-support, compared to no support. None of the devices altered the blood flow in the LAD. Cardiac power output (p<0.005) and left ventricular work (p<0.00) were also higher on Impella®-support compared to no support. CONCLUSION: Haemodynamics and blood flow to the brain and kidneys were significantly better on Impella®-support, suggesting that the Impella® is superior to the IABP in a state of ischaemia induced left ventricular failure. These data, however, needs to be confirmed in a proper clinical trial with patients in cardiogenic shock.