Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study.

OBJECTIVES: The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment. DESIGN: Prospective randomized large-animal peritoneal septic shock experiment. SETTING: Laboratory investigation. SUBJECTS: Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 µg/kg/min (LATE, n = 8). INTERVENTIONS: Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia. CONCLUSIONS: In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.

Long-term outcomes and reverse remodelling in recently diagnosed unexplained left ventricular systolic dysfunction.

AIMS: In patients with recently diagnosed non-ischaemic LV systolic dysfunction, left ventricular reverse remodelling (LVRR) and favourable prognosis has been documented in studies with short-term follow-up. The aim of our study was to assess the long-term clinical course and stability of LVRR in these patients. METHODS AND RESULTS: We prospectively studied 133 patients (37 women; 55 [interquartile range 46, 61] years) with recently diagnosed unexplained LV systolic dysfunction, with heart failure symptoms lasting <6 months and LV ejection fraction <40% persisting after at least 1 week of therapy. All patients underwent endomyocardial biopsy (EMB) at the time of diagnosis and serial echocardiographic and clinical follow-up over 5 years. LVRR was defined as the combined presence of (1) LVEF ≥ 50% or increase in LVEF ≥ 10% points and (2) decrease in LV end-diastolic diameter index (LVEDDi) ≥ 10% or (3) LVEDDi ≤ 33 mm/m2. LVRR was observed in 46% patients at 1 year, in 60% at 2 years and 50% at 5 years. Additionally, 2% of patients underwent heart transplantation and 12% experienced heart failure hospitalization. During 5-year follow-up, 23 (17%) of the study cohort died. In multivariate analysis, independent predictors of mortality were baseline right atrial size (OR 1.097, CI 1.007-1.196), logBNP level (OR 2.02, CI 1.14-3.56), and PR interval (OR 1.02, CI 1.006-1.035) (P < 0.05 for all). The number of macrophages on EMB was associated with overall survival in univariate analysis only. LVRR at 1 year of follow-up was associated with a lower rate of mortality and heart failure hospitalization (P = 0.025). In multivariate analysis, independent predictors of LVRR were left ventricular end-diastolic volume index (OR 0.97, CI 0.946-0.988), LVEF (OR 0.89, CI 0.83-0.96), and diastolic blood pressure (OR 1.04, CI 1.01-1.08) (P < 0.05 for all). CONCLUSIONS: LVRR occurs in over half of patients with recent onset unexplained LV systolic dysfunction during first 2 years of optimally guided heart failure therapy and then remains relatively stable during 5-year follow-up. Normalization of adverse LV remodelling corresponds to a low rate of mortality and heart failure hospitalizations during long-term follow-up.

Lactate: The Fallacy of Oversimplification.

Almost a quarter of a millennium after the discovery of an acidic substance in sour milk by Swedish chemist Carl Wilhelm Scheele and more than 100 years after the demonstration of a tight connection between this lactic acid and tissue hypoxia in shock, we are still surrounded by false beliefs and misunderstandings regarding this fascinating molecule. Common perceptions of lactate, the conjugate base of lactic acid, as a plain waste product of anaerobic metabolism and a marker of cellular distress could not be further from the truth. Lactate is formed and utilized continuously by our cells, even under fully aerobic conditions, in large quantities, and although marked hyperlactatemia is always a red flag in our patients, not all these conditions are life-threatening and vice versa-not all critically ill patients have hyperlactatemia. Lactate also does not promote acidosis by itself; it is not toxic, nor is it a metabolic renegade. On the contrary, it has many beneficial properties, and an interpretation of hyperlactatemia might be trickier than we tend to think. The aim of this article is to debunk some of the deeply rooted myths regarding this fascinating molecule.

The rapid detection of procalcitonin in septic serum using immunoaffinity MALDI chips.

BACKGROUND: Sepsis is a common worldwide health condition with high mortality. It is caused by a dysregulated immune response to the pathogen. Severe infections resulting in sepsis can be also determined by monitoring several bloodstream biomarkers, one of them being pro-hormone procalcitonin (PCT). PCT concentration in the bloodstream correlates well with sepsis and in severe cases increases up to a thousand times from the healthy physiological values in a short time. In this study, we developed a rapid technique for PCT detection by MALDI-TOF mass spectrometry, that uses in-situ enrichment directly on the specialized immuno MALDI chips that are utilized as MALDI plates. The method's ability to detect PCT was confirmed by comparing the results with LC-MS bottom-up workflow. The new method detects intact PCT by its m/z and uncovers its alternations in septic serum. METHODS: The MALDI chips used for the detection of PCT were prepared by ambient ion soft landing of anti-PCT antibody on an ITO glass slide. The chips were used for the development of the rapid MALDI-TOF MS method. A parallel method based on affinity enrichment on magnetic beads followed by LC-MS/MS data-dependent peptide microsequencing was used to prove PCT presence in the sample. All samples were also tested by ELISA to determine PCT concentration prior to analyzing them by mass spectrometry methods. RESULTS: The MALDI chip method was optimized using recombinant PCT spiked into the human serum. The PCT detection limit was 10 ng/mL. The optimized method was used to analyze 13 sera from patients suffering sepsis. The PCT results were confirmed by LC-MS/MS. The measurement of the intact PCT by the MALDI chip method revealed that sera of patients with severe sepsis have other forms of PCT present, which show post-processing of the primary sequence by cleavage of PCT, resulting in the formation of N and C termini fragments. CONCLUSIONS: Procalcitonin from human serum was successfully enriched and detected using immunoaffinity MALDI chips. The intact PCT was characterized in 13 septic patients. The method is more specific compared to non-MS-based immunoaffinity techniques and allows observation of different variants of PCT in septic patients.

Gut microbiome diversity of porcine peritonitis model of sepsis.

Animal models are essential in understanding of the mechanisms of sepsis moreover the development and the assessment of emerging therapies. In clinically relevant porcine model, however, a significant variability in the host response has been observed among animals. Thus, there is a strong demand to better understand the potential sources of this heterogeneity. In this study, we compared faecal microbiome composition of 12 animals. Three samples were collected at different time points from each animal. Bacteriome was subjected to 16S rDNA profiling. A significant difference in bacterial composition was associated with the season (p < 0.001) but not with the sex of the pig (p = 0.28), the timing of sample collection (p = 0.59), or interactions thereof (all p > 0.3). The season batch explained 55% of the total variance in the bacteriome diversity. The season term was highly significant from the high-resolution level of the bacterial amplicon sequencing variants up to the level of phylum. The diversity of the microbiome composition could significantly influence experimental model of sepsis, and studies are warranted to demonstrate the effects of gut microbiome diversity on the host-response. If confirmed, control of the gut microbiome should become a standard part of the pre-clinical sepsis experiments.

Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: Out-of-hospital cardiac arrest (OHCA) has poor outcome. Whether intra-arrest transport, extracorporeal cardiopulmonary resuscitation (ECPR), and immediate invasive assessment and treatment (invasive strategy) is beneficial in this setting remains uncertain. Objective: To determine whether an early invasive approach in adults with refractory OHCA improves neurologically favorable survival. Design, Setting, and Participants: Single-center, randomized clinical trial in Prague, Czech Republic, of adults with a witnessed OHCA of presumed cardiac origin without return of spontaneous circulation. A total of 256 participants, of a planned sample size of 285, were enrolled between March 2013 and October 2020. Patients were observed until death or day 180 (last patient follow-up ended on March 30, 2021). Interventions: In the invasive strategy group (n = 124), mechanical compression was initiated, followed by intra-arrest transport to a cardiac center for ECPR and immediate invasive assessment and treatment. Regular advanced cardiac life support was continued on-site in the standard strategy group (n = 132). Main Outcomes and Measures: The primary outcome was survival with a good neurologic outcome (defined as Cerebral Performance Category [CPC] 1-2) at 180 days after randomization. Secondary outcomes included neurologic recovery at 30 days (defined as CPC 1-2 at any time within the first 30 days) and cardiac recovery at 30 days (defined as no need for pharmacological or mechanical cardiac support for at least 24 hours). Results: The trial was stopped at the recommendation of the data and safety monitoring board when prespecified criteria for futility were met. Among 256 patients (median age, 58 years; 44 [17%] women), 256 (100%) completed the trial. In the main analysis, 39 patients (31.5%) in the invasive strategy group and 29 (22.0%) in the standard strategy group survived to 180 days with good neurologic outcome (odds ratio [OR], 1.63 [95% CI, 0.93 to 2.85]; difference, 9.5% [95% CI, -1.3% to 20.1%]; P = .09). At 30 days, neurologic recovery had occurred in 38 patients (30.6%) in the invasive strategy group and in 24 (18.2%) in the standard strategy group (OR, 1.99 [95% CI, 1.11 to 3.57]; difference, 12.4% [95% CI, 1.9% to 22.7%]; P = .02), and cardiac recovery had occurred in 54 (43.5%) and 45 (34.1%) patients, respectively (OR, 1.49 [95% CI, 0.91 to 2.47]; difference, 9.4% [95% CI, -2.5% to 21%]; P = .12). Bleeding occurred more frequently in the invasive strategy vs standard strategy group (31% vs 15%, respectively). Conclusions and Relevance: Among patients with refractory out-of-hospital cardiac arrest, the bundle of early intra-arrest transport, ECPR, and invasive assessment and treatment did not significantly improve survival with neurologically favorable outcome at 180 days compared with standard resuscitation. However, the trial was possibly underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT01511666.

Modeling sepsis, with a special focus on large animal models of porcine peritonitis and bacteremia.

Infectious diseases, which often result in deadly sepsis or septic shock, represent a major global health problem. For understanding the pathophysiology of sepsis and developing new treatment strategies, reliable and clinically relevant animal models of the disease are necessary. In this review, two large animal (porcine) models of sepsis induced by either peritonitis or bacteremia are introduced and their strong and weak points are discussed in the context of clinical relevance and other animal models of sepsis, with a special focus on cardiovascular and immune systems, experimental design, and monitoring. Especially for testing new therapeutic strategies, the large animal (porcine) models represent a more clinically relevant alternative to small animal models, and the findings obtained in small animal (transgenic) models should be verified in these clinically relevant large animal models before translation to the clinical level.

Surgical repair of a coronary artery aneurysm associated with coronary artery fistula - a case report.

Coronary artery aneurysm is a relatively rare disorder that is usually discovered as a secondary finding in patients undergoing coronary artery angiography. Coronary artery fistulas are relatively more frequent than rare aneurysms and are often associated with other cardiac abnormalities. The etiology of aneurysms is mostly atherosclerotic, and they are less frequently associated with other acquired or congenital diseases, such as Kawasaki disease, connective tissue diseases, septic emboli, arteritis, and iatrogenic disease. We report a 70-year-old woman with a rare combination of a coronary artery aneurysm associated with a coronary artery fistula, which drained into the pulmonary artery. The diagnosis of our patient was made by selective coronary angiography and confirmed by computed tomography angiography. The patient was treated surgically because of the symptomatic course of the disease.

SOFA Score, Hemodynamics and Body Temperature Allow Early Discrimination between Porcine Peritonitis-Induced Sepsis and Peritonitis-Induced Septic Shock.

Porcine model of peritonitis-induced sepsis is a well-established clinically relevant model of human disease. Interindividual variability of the response often complicates the interpretation of findings. To better understand the biological basis of the disease variability, the progression of the disease was compared between animals with sepsis and septic shock. Peritonitis was induced by inoculation of autologous feces in fifteen anesthetized, mechanically ventilated and surgically instrumented pigs and continued for 24 h. Cardiovascular and biochemical parameters were collected at baseline (just before peritonitis induction), 12 h, 18 h and 24 h (end of the experiment) after induction of peritonitis. Analysis of multiple parameters revealed the earliest significant differences between sepsis and septic shock groups in the sequential organ failure assessment (SOFA) score, systemic vascular resistance, partial pressure of oxygen in mixed venous blood and body temperature. Other significant functional differences developed later in the course of the disease. The data indicate that SOFA score, hemodynamical parameters and body temperature discriminate early between sepsis and septic shock in a clinically relevant porcine model. Early pronounced alterations of these parameters may herald a progression of the disease toward irreversible septic shock.

Evaluation of Mesenchymal Stem Cell Therapy for Sepsis: A Randomized Controlled Porcine Study.

Background: Treatment with mesenchymal stem cells (MSCs) has elicited considerable interest as an adjunctive therapy in sepsis. However, the encouraging effects of experiments with MSC in rodents have not been adequately studied in large-animal models with better relevance to human sepsis. Objectives: Here, we aimed to assess safety and efficacy of bone marrow-derived MSCs in a clinically relevant porcine model of progressive peritonitis-induced sepsis. Methods: Thirty-two anesthetized, mechanically ventilated, and instrumented pigs were randomly assigned into four groups (n = 8 per group): (1) sham-operated group (CONTROL); (2) sham-operated group treated with MSCs (MSC-CONTROL); (3) sepsis group with standard supportive care (SEPSIS); and (4) sepsis group treated with MSCs (MSC-SEPSIS). Peritoneal sepsis was induced by inoculating cultivated autologous feces. MSCs (1 × 106/kg) were administered intravenously at 6 h after sepsis induction. Results: Before, 12, 18, and 24 h after the induction of peritonitis, we measured systemic, regional, and microvascular hemodynamics, multiple-organ functions, mitochondrial energy metabolism, systemic immune-inflammatory response, and oxidative stress. Administration of MSCs in the MSC-CONTROL group did not elicit any measurable acute effects. Treatment of septic animals with MSCs failed to mitigate sepsis-induced hemodynamic alterations or the gradual rise in Sepsis-related organ failure assessment scores. MSCs did not confer any protection against sepsis-mediated cellular myocardial depression and mitochondrial dysfunction. MSCs also failed to modulate the deregulated immune-inflammatory response. Conclusion: Intravenous administration of bone marrow-derived MSCs to healthy animals was well-tolerated. However, in this large-animal, clinically relevant peritonitis-induced sepsis model, MSCs were not capable of reversing any of the sepsis-induced disturbances in multiple biological, organ, and cellular systems.

Back to Basics: Recognition of Sepsis with New Definition.

Patients with serious infections at risk of deterioration represent highly challenging clinical situations, and in particular for junior doctors. A comprehensive clinical examination that integrates the assessment of vital signs, hemodynamics, and peripheral perfusion into clinical decision making is key to responding promptly and effectively to evolving acute medical illnesses, such as sepsis or septic shock. Against this background, the new concept of sepsis definition may provide a useful link between junior doctors and consultant decision making. The purpose of this article is to introduce the updated definition of sepsis and suggest its practical implications, with particular emphasis on integrative clinical assessment, allowing for the rapid identification of patients who are at risk of further deterioration.

Extracorporeal removal techniques in toxicology: part 1.

Supporting clearance of a toxic substance by an extracorporeal removal technique is one of the advanced treatment methods applied in poisoned patient management. General indications stem from toxicokinetics of the poison while individual indications are determined by poisoning severity. The first part of this review deals in detail with particular options of extracorporeal treatment in toxicology and also with its specific application when treating lithium and salicylates poisoning or dabigatran overdose. The aim of this review is to facilitate the clinicians and nephrologists decision making whether to indicate this invasive procedure, to communicate and summarize the existing recommendations and to highlight the most important ways of how to treat poisoning by specific toxic substances.

Extracorporeal removal techniques in toxicology: part 2.

The second part of the review deals in detail with the diagnostics and treatment of toxic alcohols poisoning and management and indication of extracorporeal removal techniques in intoxication with other drugs, theophylline, valproic acid, metformin and metformin associated lactic acidosis, respectively. The extracorporeal treatment enhances the clearance of the toxin and corrects patients metabolic disturbances as well. It is necessary to use this treatment in severe intoxications. Indication of this invasive procedure falls within clinicians and nephrologists competence being advised by a toxicologist. This review could help make fast decisions.

Intravenous fluid therapy in acutely ill patients for non-intensivists.

Intravenous fluid therapy is the most frequent therapeutic intervention in acutely hospitalized patients. They are administered in order to resuscitate the circulation in hypovolemia-associated shock states, to compensate for an impending or existing fluid extracellular deficit, or as a maintenance infusion if the patient is incapable of taking fluid by other means. Any fluid should be prescribed with the same caution as with any other drug. Errors in fluid therapy adversely affect patient - centered outcome. This may be the result of an incorrectly selected amount or inappropriate fluid composition for a given clinical situation. Prescribing intravenous fluids is a complex process involving a decision on the type, composition, dose, rate and possible toxicity of the particular solution. Balanced crystalloid solutions are the first choice for most acute conditions. The need for fluids dynamically changes over time in acutely ill patients. Uncontrolled cumulative positive balance is associated with substantial morbidity and mortality.

Vagus Nerve Stimulation Attenuates Multiple Organ Dysfunction in Resuscitated Porcine Progressive Sepsis.

OBJECTIVES: To investigate the potential benefits of vagus nerve stimulation in a clinically-relevant large animal model of progressive sepsis. DESIGN: Prospective, controlled, randomized trial. SETTING: University animal research laboratory. SUBJECTS: Twenty-five domestic pigs were divided into three groups: 1) sepsis group (eight pigs), 2) sepsis + vagus nerve stimulation group (nine pigs), and 3) control sham group (eight pigs). INTERVENTIONS: Sepsis was induced by cultivated autologous feces inoculation in anesthetized, mechanically ventilated, and surgically instrumented pigs and followed for 24 hours. Electrical stimulation of the cervical vagus nerve was initiated 6 hours after the induction of peritonitis and maintained throughout the experiment. MEASUREMENTS AND MAIN RESULTS: Measurements of hemodynamics, electrocardiography, biochemistry, blood gases, cytokines, and blood cells were collected at baseline (just before peritonitis induction) and at the end of the in vivo experiment (24 hr after peritonitis induction). Subsequent in vitro analyses addressed cardiac contractility and calcium handling in isolated tissues and myocytes and analyzed mitochondrial function by ultrasensitive oxygraphy. Vagus nerve stimulation partially or completely prevented the development of hyperlactatemia, hyperdynamic circulation, cellular myocardial depression, shift in sympathovagal balance toward sympathetic dominance, and cardiac mitochondrial dysfunction, and reduced the number of activated monocytes. Sequential Organ Failure Assessment scores and vasopressor requirements significantly decreased after vagus nerve stimulation. CONCLUSIONS: In a clinically-relevant large animal model of progressive sepsis, vagus nerve stimulation was associated with a number of beneficial effects that resulted in significantly attenuated multiple organ dysfunction and reduced vasopressor and fluid resuscitation requirements. This suggests that vagus nerve stimulation might provide a significant therapeutic potential that warrants further thorough investigation.

Occlusion of Epicardial Coronary Arteries by Localized Pericardial Calcification.

Localized pericardial calcification is a relatively rare finding of often unknown etiology. We present the case of a 68-year-old man who was found to have bulky pericardial calcification, resulting in external compression of epicardial coronary arteries. (Level of Difficulty: Beginner.).

Cellular Mechanisms of Myocardial Depression in Porcine Septic Shock.

The complex pathogenesis of sepsis and septic shock involves myocardial depression, the pathophysiology of which, however, remains unclear. In this study, cellular mechanisms of myocardial depression were addressed in a clinically relevant, large animal (porcine) model of sepsis and septic shock. Sepsis was induced by fecal peritonitis in eight anesthetized, mechanically ventilated, and instrumented pigs of both sexes and continued for 24 h. In eight control pigs, an identical experiment but without sepsis induction was performed. In vitro analysis of cardiac function included measurements of action potentials and contractions in the right ventricle trabeculae, measurements of sarcomeric contractions, calcium transients and calcium current in isolated cardiac myocytes, and analysis of mitochondrial respiration by ultrasensitive oxygraphy. Increased values of modified sequential organ failure assessment score and serum lactate levels documented the development of sepsis/septic shock, accompanied by hyperdynamic circulation with high heart rate, increased cardiac output, peripheral vasodilation, and decreased stroke volume. In septic trabeculae, action potential duration was shortened and contraction force reduced. In septic cardiac myocytes, sarcomeric contractions, calcium transients, and L-type calcium current were all suppressed. Similar relaxation trajectory of the intracellular calcium-cell length phase-plane diagram indicated unchanged calcium responsiveness of myofilaments. Mitochondrial respiration was diminished through inhibition of Complex II and Complex IV. Defective calcium handling with reduced calcium current and transients, together with inhibition of mitochondrial respiration, appears to represent the dominant cellular mechanisms of myocardial depression in porcine septic shock.

Mesenchymal Stem Cells in Sepsis and Associated Organ Dysfunction: A Promising Future or Blind Alley?

Sepsis, newly defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, is the most common cause of death in ICUs and one of the principal causes of death worldwide. Although substantial progress has been made in the understanding of fundamental mechanisms of sepsis, translation of these advances into clinically effective therapies has been disappointing. Given the extreme complexity of sepsis pathogenesis, the paradigm "one disease, one drug" is obviously flawed and combinations of multiple targets that involve early immunomodulation and cellular protection are needed. In this context, the immune-reprogramming properties of cell-based therapy using mesenchymal stem cells (MSC) represent an emerging therapeutic strategy in sepsis and associated organ dysfunction. This article provides an update of the current knowledge regarding MSC in preclinical models of sepsis and sepsis-induced acute kidney injury. Recommendations for further translational research in this field are discussed.

Surgical Revascularisation in the Early Phase of ST-Segment Elevation Myocardial Infarction: Haemodynamic Status is More Important Than the Timing of the Operation.

BACKGROUND: Surgical revascularisation in patients with acute myocardial infarction with ST-Segment Elevation (STEMI) is usually considered as a second choice when direct angioplasty/stent fails. However, improvements in surgical technique and postoperative care may justify coronary artery bypass grafting (CABG) in STEMI. METHODS: This was a retrospective analysis of prospectively gathered data of 135 patients with acute STEMI, treated with CABG in our department from February 2008 to December 2012. Patients were divided into two groups - operated up to 6 hours (35 patients) and 6 to 24hours (100 patients) from onset of symptoms. RESULTS: Preoperatively, 18 (13%) patients were in cardiogenic shock, 10 (7.4%) had mechanical ventilation, and 36 (27%) had intra-aortic balloon counterpulsation (IABC). Mean number of distal anastomoses was 3.3 (range, 1 to 5), cardiopulmonary bypass time 122.7+52.6minutes. In hospital (30-day) mortality was 8.1% (11 patients) with no significant difference in both groups (p=0.541); 45 (33%) patients had one MACE, again with no difference in both groups (p=0.89). Risk factor analysis revealed that Killip class at admission, cardiogenic shock, preoperative need for catecholamines, ventilation and low ejection fraction are risk factors for early mortality. CONCLUSIONS: Acute CABG in patients with STEMI can be performed with good results. Risk factors for early mortality and morbidity are cardiogenic shock, poor haemodynamic status and impaired ejection fraction. Time from infarction to reperfusion did not influence the results.

Fenotipo del engrosamiento intimal patológico: no tan inocente como se pensaba. Estudio de la histología virtual de una serie de casos con ecografía intravascular 3D / Pathologic intimal thickening plaque phenotype: not as innocent as previously thought. A serial 3D intravascular ultrasound virtual histology study

Introducción y objetivos: Se ha considerado que el engrosamiento intimal patológico (EIP) es un fenotipo de placa benigno. Se presentan los cambios fenotípicos de la placa en un estudio comparativo entre situación basal y seguimiento mediante un estudio de reconstrucción histológica virtual por ecografía intravascular. Métodos: Se estudió a 61 pacientes con enfermedad coronaria estable del ensayo HEAVEN (89 pacientes aleatorizados al tratamiento estándar con estatinas o atorvastatina 80 mg y ezetimiba 10 mg) por ecografía intravascular seriada de las arterias no culpables. Se compararon los cambios examinando al inicio del estudio y durante el seguimiento 693 segmentos de 5 mm de longitud mediante una nueva puntuación de riesgo, la Liverpool Active Plaque Score (LAPS), los parámetros de la placa y la composición de esta. Resultados: El EIP es el tipo que mostró mayor aumento de la puntuación de riesgo y, junto con las placas fibrosas, también de la LAPS. El core necrótico (CN) próximo a la luz aumentó tanto en las placas con EIP (22 ± 51,7; p = 0,0001) como en las placas fibrosas (17,9 ± 42,6; p = 0,004), pero disminuyó en el fibroateroma de capa fina (FCF) (–15,14 ± 52,2; p = 0,001). El EIP es el tipo de placa de fibroateroma de capa no fina con mayor probabilidad de transformación a FCF durante el seguimiento (el 11% del total de FCF hallados durante el seguimiento y el 35,9% de los FCF de nueva aparición), pero también el que mostró (junto con las placas fibrosas) menor estabilidad durante el tratamiento hipolipemiante (el 24,7% de los EIP y el 24,5% de las placas fibrosas se mantuvieron estables). Conclusiones: En 1 año de seguimiento, el EIP fue el fenotipo de placa más dinámico y se asoció a un aumento de la puntuación de riesgo y de la LAPS (junto con la placa fibrosa), el porcentaje de CN (junto con la placa fibrosa) y el CN próximo a la luz, a pesar de una pequeña reducción del volumen de la placa durante el tratamiento hipolipemiante. El EIP fue el principal origen de los nuevos segmentos con FCF (AU)

Introduction and objectives: Pathologic intimal thickening (PIT) has been considered a benign plaque phenotype. We report plaque phenotypic changes in a baseline/follow-up intravascular ultrasound-based virtual histology study. Methods: A total of 61 patients with stable coronary artery disease were analyzed from the HEAVEN trial (89 patients randomized between routine statin therapy vs atorvastatin 80 mg and ezetimibe 10 mg) with serial intravascular ultrasound imaging of non-culprit vessels. We compared changes in 693 baseline and follow-up 5-mm long segments in a novel risk score, Liverpool Active Plaque Score (LAPS), plaque parameters, and plaque composition. Results: The PIT showed the highest increase of risk score and, with fibrous plaque, also the LAPS. Necrotic core (NC) abutting to the lumen increased in PIT (22 ± 51.7; P = .0001) and in fibrous plaque (17.9 ± 42.6; P = .004) but decreased in thin cap fibroatheroma (TCFA) (-15.14 ± 52.2; P = .001). The PIT was the most likely of all non-thin cap fibroatheroma plaque types to transform into TCFA at follow-up (11% of all TCFA found during follow-up and 35.9% of newly-developed TCFA), but showed (together with fibrous plaque) the lowest stability during lipid-lowering therapy (24.7% of PIT remained PIT and 24.5% of fibrous plaque remained fibrous plaque). Conclusions: Over the 1-year follow-up, PIT was the most dynamic of the plaque phenotypes and was associated with an increase of risk score and LAPS (together with fibrous plaque), NC percentage (together with fibrous plaque) and NC abutting to the lumen, despite a small reduction of plaque volume during lipid-lowering therapy. The PIT was the main source for new TCFA segments (AU)