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.

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.

Invasive mechanical ventilation in cardiogenic shock complicating acute myocardial infarction: A contemporary Danish cohort analysis.

PURPOSE: Invasive mechanical ventilation (IMV) is widely used in patients with cardiogenic shock following acute myocardial infarction (AMICS), but evidence to guide practice remains sparse. We sought to evaluate trends in the rate of IMV utilization, applied settings, and short term-outcome of a contemporary cohort of AMICS patients treated with IMV according to out-of-hospital cardiac arrest (OHCA) at admission. METHODS: Consecutive AMICS patients receiving IMV in an intensive care unit (ICU) at two tertiary centres between 2010 and 2017. Data were analysed in relation to OHCA. RESULTS: A total of 1274 mechanically ventilated AMICS patients were identified, 682 (54%) with OHCA. Frequency of IMV increased during the study period, primarily due to higher occurrence of OHCA admissions. Among 566 patients with complete ventilator data, positive-end-expiratory pressure, inspired oxygen fraction, and minute ventilation during the initial 24 h in ICU were monitored. No differences were observed between 30-day survivors and non-survivors with OHCA. In non-OHCA, these ventilator requirements were significantly higher among 30-day non-survivors (P for all<0.05), accompanied by a lower PaO2/FiO2 ratio (median 143 vs. 230, P < 0.001) and higher arterial lactate levels (median 3.5 vs. 1.5 mmol/L, P < 0.001) than survivors. Physiologically normal PaO2 and pCO2 levels were achieved in all patients irrespective of 30-day survival and OHCA status. CONCLUSION: In the present contemporary cohort of AMICS patients, physiologically normal blood gas values were achieved both in OHCA and non-OHCA in the early phase of admission. However, increased demand of ventilatory support was associated with poorer survival only in non-OHCA patients.

DIFFERENCES IN MANAGEMENT AND PROGNOSTICATION OF CARDIOGENIC SHOCK PATIENTS IN THE PRESENCE AND ABSENCE OF OUT-OF-HOSPITAL CARDIAC ARREST.

ABSTRACT: Background: The clinical spectrum of acute myocardial infarction complicated by cardiogenic shock (AMICS) varies. Out-of-hospital cardiac arrest (OHCA) can be the first sign of cardiac failure, whereas others present with various degrees of hemodynamic instability (non-OHCA). The aim of the present study was to explore differences in prehospital management and characteristics of survivors and nonsurvivors in AMICS patients with OHCA or non-OHCA. Methods: Data analysis was based on patient data from the RETROSHOCK cohort comprising consecutive AMICS patients admitted to two tertiary cardiac centers between 2010 and 2017. Results: 1,716 AMICS patients were included and 42% presented with OHCA. Mortality in OHCA patients was 47% versus 57% in the non-OHCA group. Almost all OHCA patients were intubated before admission (96%). In the non-OHCA group, prehospital intubation (25%) was associated with a better survival ( P < 0.001). Lactate level on admission demonstrated a linear relationship with mortality in OHCA patients. In non-OHCA, probability of death was higher for any given lactate level <12 mmol/L compared with OHCA. However, a lactate level >7 mmol/L in non-OHCA did not increase mortality odds any further. Conclusion: Mortality was almost doubled for any admission lactate level up to 7 mmol/L in non-OHCA patients. Above this level, mortality remained unchanged in non-OHCA patients but continued to increase in OHCA patients. Prehospital intubation was performed in almost all OHCA patients but only in one of four patients without OHCA. Early intubation in non-OHCA patients was associated with a better outcome.

Thiamine for the Treatment of Cardiac Arrest-Induced Neurological Injury: A Randomized, Blinded, Placebo-Controlled Experimental Study.

Background Thiamine supplementation has demonstrated protective effects in a mouse model of cardiac arrest. The aim of this study was to investigate the neuroprotective effects of thiamine in a clinically relevant large animal cardiac arrest model. The hypothesis was that thiamine reduces neurological injury evaluated by neuron-specific enolase levels. Methods and Results Pigs underwent myocardial infarction and subsequently 9 minutes of untreated cardiac arrest. Twenty minutes after successful resuscitation, the pigs were randomized to treatment with either thiamine or placebo. All pigs underwent 40 hours of intensive care and were awakened for assessment of functional neurological outcome up until 9 days after cardiac arrest. Nine pigs were included in both groups, with 8 in each group surviving the entire intensive care phase. Mean area under the curve for neuron-specific enolase was similar between groups, with 81.5 µg/L per hour (SD, 20.4) in the thiamine group and 80.5 µg/L per hour (SD, 18.3) in the placebo group, with an absolute difference of 1.0 (95% CI, -57.8 to 59.8; P=0.97). Likewise, there were no absolute difference in neurological deficit score at the end of the protocol (2 [95% CI, -38 to 42]; P=0.93). There was no absolute mean group difference in lactate during the intensive care period (1.1 mmol/L [95% CI, -0.5 to 2.7]; P=0.16). Conclusions In this randomized, blinded, placebo-controlled trial using a pig cardiac arrest model with myocardial infarction and long intensive care and observation for 9 days, thiamine showed no effect in changes to functional neurological outcome or serum levels of neuron-specific enolase. Thiamine treatment had no effect on lactate levels after successful resuscitation.

Effect of calcium in patients with pulseless electrical activity and electrocardiographic characteristics potentially associated with hyperkalemia and ischemia-sub-study of the Calcium for Out-of-hospital Cardiac Arrest (COCA) trial.

OBJECTIVE: The Calcium for Out-of-hospital Cardiac Arrest (COCA) trial was recently conducted and published. This pre-planned sub-study evaluated the effect of calcium in patients with pulseless electrical activity (PEA) including subgroup analyses based on electrocardiographic characteristics potentially associated with hyperkalemia and ischemia. METHODS: Patients aged ≥ 18 years were included if they had a non-traumatic out-of-hospital cardiac arrest and received adrenaline. The trial drug consisted of calcium chloride (5 mmol) or saline placebo given after the first, and again after the second, dose of adrenaline for a maximum of two doses. This sub-study analyzed patients with PEA as their last known rhythm prior to receiving the trial drug. Outcomes were return of spontaneous circulation and survival at 30 days. RESULTS: 104 patients were analyzed. In the calcium group, 9 patients (20 %) achieved return of spontaneous circulation vs 23 patients (39 %) in the placebo group (risk ratio 0.51; 95 %CI 0.26, 1.00). Subgroup analyses based on electrocardiographic characteristics potentially associated with hyperkalemia and ischemia showed similar results. At 30 days, 1 patient (2.2 %) was alive in the calcium group while 8 patients (13.6 %) were alive in the placebo group (risk ratio 0.16; 95 %CI 0.02, 1.26). CONCLUSION: In adults with out-of-hospital cardiac arrest presenting with PEA, effect estimates suggested harm of calcium administration as compared to placebo but with wide confidence intervals. Results were consistent for patients with electrocardiographic characteristics potentially associated with hyperkalemia and ischemia. The results do not support calcium administration based strictly on electrocardiographic findings seen during out-of-hospital cardiac arrest.

Cerebral monitoring in a pig model of cardiac arrest with 48 h of intensive care.

BACKGROUND: Neurological injury is the primary cause of death after out-of-hospital cardiac arrest. There is a lack of studies investigating cerebral injury beyond the immediate post-resuscitation phase in a controlled cardiac arrest experimental setting. METHODS: The aim of this study was to investigate temporal changes in measures of cerebral injury and metabolism in a cardiac arrest pig model with clinically relevant post-cardiac arrest intensive care. A cardiac arrest group (n = 11) underwent 7 min of no-flow and was compared with a sham group (n = 6). Pigs underwent intensive care with 24 h of hypothermia at 33 °C. Blood markers of cerebral injury, cerebral microdialysis, and intracranial pressure (ICP) were measured. After 48 h, pigs underwent a cerebral MRI scan. Data are presented as median [25th; 75th percentiles]. RESULTS: Return of spontaneous circulation was achieved in 7/11 pigs. Time to ROSC was 4.4 min [4.2; 10.9]. Both NSE and NfL increased over time (p < 0.001), and were higher in the cardiac arrest group at 48 h (NSE 4.2 µg/L [2.4; 6.1] vs 0.9 [0.7; 0.9], p < 0.001; NfL 63 ng/L [35; 232] vs 29 [21; 34], p = 0.02). There was no difference in ICP at 48 h (17 mmHg [14; 24] vs 18 [13; 20], p = 0.44). The cerebral lactate/pyruvate ratio had secondary surges in 3/7 cardiac arrest pigs after successful resuscitation. Apparent diffusion coefficient was lower in the cardiac arrest group in white matter cortex (689 × 10-6 mm2/s [524; 765] vs 800 [799; 815], p = 0.04) and hippocampus (854 [834; 910] vs 1049 [964; 1180], p = 0.03). N-Acetylaspartate was lower on MR spectroscopy in the cardiac arrest group (- 17.2 log [- 17.4; - 17.0] vs - 16.9 [- 16.9; - 16.9], p = 0.03). CONCLUSIONS: We have developed a clinically relevant cardiac arrest pig model that displays cerebral injury as marked by NSE and NfL elevations, signs of cerebral oedema, and reduced neuron viability. Overall, the burden of elevated ICP was low in the cardiac arrest group. A subset of pigs undergoing cardiac arrest had persisting metabolic disturbances after successful resuscitation.

Effect of calcium vs. placebo on long-term outcomes in patients with out-of-hospital cardiac arrest.

OBJECTIVE: The Calcium for Out-of-hospital Cardiac Arrest (COCA) trial was a randomized, placebo-controlled, double-blind trial of calcium for out-of-hospital cardiac arrest. The primary and secondary outcomes have been reported previously. This article describes the long-term outcomes of the trial. METHODS: Patients aged ≥18 years were included if they had a non-traumatic out-of-hospital cardiac arrest during which they received adrenaline. The trial drug consisted of calcium chloride (5 mmol) or saline placebo given after the first dose of adrenaline and again after the second dose of adrenaline for a maximum of two doses. This article presents pre-specified analyses of 6-month and 1-year outcomes for survival, survival with a favorable neurological outcome (modified Rankin Scale of 3 or less), and health-related quality of life. RESULTS: A total of 391 patients were analyzed. At 1 year, 9 patients (4.7%) were alive in the calcium group while 18 (9.1%) were alive in the placebo group (risk ratio 0.51; 95% confidence interval 0.24, 1.09). At 1 year, 7 patients (3.6%) were alive with a favorable neurological outcome in the calcium group while 17 (8.6%) were alive with a favorable neurological outcome in the placebo group (risk ratio 0.42; 95% confidence interval 0.18, 0.97). Outcomes for health-related quality of life likewise suggested harm of calcium but results were imprecise with wide confidence intervals. CONCLUSIONS: Effect estimates remained constant over time suggesting harm of calcium but with wide confidence intervals. The results do not support calcium administration during out-of-hospital cardiac arrest. TRIAL REGISTRATION: ClinicalTrials.gov-number, NCT04153435.

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.

Alignment of strontium hexaferrite, by cold compaction of anisotropic non-magnetically interacting crystallites.

Cold compacted, anisotropic shaped non-magnetically interacting precursors are used to achieve aligned strontium hexaferrites. The simple process of dry mixing platy hematite and/or rod-like goethite with strontium carbonate removes the need for external magnetic fields or high temperatures during compaction to assist in alignment. The calcined strontium hexaferrite pellets all displayed preferred orientation and high levels of phase purity (>99 wt%). The mix of goethite and strontium carbonate achieved the highest degree of magnetic alignment with Mr/Ms reaching 0.83(1) obtained by vibrating sample magnetometry. The magnetic data were supported by examining crystallographic alignment using powder X-ray diffraction as well as 2D texture synchrotron analysis.

Cardiac Arrest in Pigs With 48 hours of Post-Resuscitation Care Induced by 2 Methods of Myocardial Infarction: A Methodological Description.

Background Systematic reviews have disclosed a lack of clinically relevant cardiac arrest animal models. The aim of this study was to develop a cardiac arrest model in pigs encompassing relevant cardiac arrest characteristics and clinically relevant post-resuscitation care. Methods and Results We used 2 methods of myocardial infarction in conjunction with cardiac arrest. One group (n=7) had a continuous coronary occlusion, while another group (n=11) underwent balloon-deflation during arrest and resuscitation with re-inflation after return of spontaneous circulation. A sham group was included (n=6). All groups underwent 48 hours of intensive care including 24 hours of targeted temperature management. Pigs underwent invasive hemodynamic monitoring. Left ventricular function was assessed by pressure-volume measurements. The proportion of pigs with return of spontaneous circulation was 43% in the continuous infarction group and 64% in the deflation-reinflation group. In the continuous infarction group 29% survived the entire protocol while 55% survived in the deflation-reinflation group. Both cardiac arrest groups needed vasopressor and inotropic support and pressure-volume measurements showed cardiac dysfunction. During rewarming, systemic vascular resistance decreased in both cardiac arrest groups. Median [25%;75%] troponin-I 48 hours after return of spontaneous circulation, was 88 973 ng/L [53 124;99 740] in the continuous infarction group, 19 661 ng/L [10 871;23 209] in the deflation-reinflation group, and 1973 ng/L [1117;1995] in the sham group. Conclusions This article describes a cardiac arrest pig model with myocardial infarction, targeted temperature management, and clinically relevant post-cardiac arrest care. We demonstrate 2 methods of inducing myocardial ischemia with cardiac arrest resulting in post-cardiac arrest organ injury including cardiac dysfunction and cerebral injury.

Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: It is unclear whether administration of calcium has a beneficial effect in patients with cardiac arrest. Objective: To determine whether administration of calcium during out-of-hospital cardiac arrest improves return of spontaneous circulation in adults. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial included 397 adult patients with out-of-hospital cardiac arrest and was conducted in the Central Denmark Region between January 20, 2020, and April 15, 2021. The last 90-day follow-up was on July 15, 2021. Interventions: The intervention consisted of up to 2 intravenous or intraosseous doses with 5 mmol of calcium chloride (n = 197) or saline (n = 200). The first dose was administered immediately after the first dose of epinephrine. Main Outcomes and Measures: The primary outcome was sustained return of spontaneous circulation. The secondary outcomes included survival and a favorable neurological outcome (modified Rankin Scale score of 0-3) at 30 days and 90 days. Results: Based on a planned interim analysis of 383 patients, the steering committee stopped the trial early due to concerns about harm in the calcium group. Of 397 adult patients randomized, 391 were included in the analyses (193 in the calcium group and 198 in the saline group; mean age, 68 [SD, 14] years; 114 [29%] were female). There was no loss to follow-up. There were 37 patients (19%) in the calcium group who had sustained return of spontaneous circulation compared with 53 patients (27%) in the saline group (risk ratio, 0.72 [95% CI, 0.49 to 1.03]; risk difference, -7.6% [95% CI, -16% to 0.8%]; P = .09). At 30 days, 10 patients (5.2%) in the calcium group and 18 patients (9.1%) in the saline group were alive (risk ratio, 0.57 [95% CI, 0.27 to 1.18]; risk difference, -3.9% [95% CI, -9.4% to 1.3%]; P = .17). A favorable neurological outcome at 30 days was observed in 7 patients (3.6%) in the calcium group and in 15 patients (7.6%) in the saline group (risk ratio, 0.48 [95% CI, 0.20 to 1.12]; risk difference, -4.0% [95% CI, -8.9% to 0.7%]; P = .12). Among the patients with calcium values measured who had return of spontaneous circulation, 26 (74%) in the calcium group and 1 (2%) in the saline group had hypercalcemia. Conclusions and Relevance: Among adults with out-of-hospital cardiac arrest, treatment with intravenous or intraosseous calcium compared with saline did not significantly improve sustained return of spontaneous circulation. These results do not support the administration of calcium during out-of-hospital cardiac arrest in adults. Trial Registration: ClinicalTrials.gov Identifier: NCT04153435.

Association of Body Mass Index with Mortality in Patients with Cardiogenic Shock following Acute Myocardial Infarction: A Contemporary Danish Cohort Analysis.

AIMS: The obesity paradox suggests a better prognosis in overweight or obese patients with heart failure and acute myocardial infarction (AMI) than patients with normal weight. Few studies have investigated the association between BMI and mortality in patients with AMI complicated by cardiogenic shock (AMICS). The aim of this study was to evaluate the association between BMI and 30-day mortality in patients with AMICS. METHODS AND RESULTS: A retrospective study of 1,716 patients with AMICS treated at 2 tertiary centers in south-eastern Denmark between 2010 and 2017. Patients undergoing revascularization and who were admitted to the intensive care unit were included (n = 1,216). BMI was available in 1,017 patients (83.6%). Patients were divided according to the WHO classification as normal weight BMI <24.9 kg/m2 (n = 453), overweight BMI 25-29.9 kg/m2 (n = 391), obese class 1 BMI 30-34.9 kg/m2 (n = 131), and obese class 2 + 3 BMI >35 kg/m2 (n = 42). Differences in baseline characteristics, in-hospital treatment, and the primary outcome of all-cause mortality at 30 days were examined. Obese patients had more comorbidities such as diabetes, hypertension, and dyslipidemia than patients with normal weight. Need for renal replacement therapy was higher among obese patients (normal weight, 19% vs. obese class 2 + 3, 35%, p = 0.02); otherwise, no difference in management was found. No difference in 30-day mortality was observed between groups (normal weight 44%, overweight 38%, obese class 1 41%, and obese class 2 + 3 45% at 30 days; ns). CONCLUSIONS: Thirty-day mortality in patients with AMICS was not associated with the BMI category. Thus, evidence of an "obesity paradox" was not observed in this contemporary cohort of patients with AMICS in Denmark.

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.

The Vasoactive Mas Receptor in Essential Hypertension.

The renin-angiotensin-aldosterone system (RAAS) has been studied extensively, and with the inclusion of novel components, it has become evident that the system is much more complex than originally anticipated. According to current knowledge, there are two main axes of the RAAS, which counteract each other in terms of vascular control: The classical vasoconstrictive axis, renin/angiotensin-converting enzyme/angiotensin II/angiotensin II receptor type 1 (AT1R), and the opposing vasorelaxant axis, angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptor (MasR). An abnormal activity within the system constitutes a hallmark in hypertension, which is a global health problem that predisposes cardiovascular and renal morbidities. In particular, essential hypertension predominates in the hypertensive population of more than 1.3 billion humans worldwide, and yet, the pathophysiology behind this multifactorial condition needs clarification. While commonly applied pharmacological strategies target the classical axis of the RAAS, discovery of the vasoprotective effects of the opposing, vasorelaxant axis has presented encouraging experimental evidence for a new potential direction in RAAS-targeted therapy based on the G protein-coupled MasR. In addition, the endogenous MasR agonist angiotensin-(1-7), peptide analogues, and related molecules have become the subject of recent studies within this field. Nevertheless, the clinical potential of MasR remains unclear due to indications of physiological-biased activities of the RAAS and interacting signaling pathways.