Refractory Ventricle Arrhythmias Alternating with Pulseless Electrical Activity in a Young Woman Rescued by Extracorporeal Cardiopulmonary Resuscitation.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) is a challenging approach for treating refractory out-of-hospital cardiac arrest (OHCA). CASE PRESENTATION: The authors describe a case of a 40-year-old Caucasian female who suffered from refractory OHCA, was admitted to a hospital while receiving ongoing cardiopulmonary resuscitation, and was connected to venoarterial extracorporeal membrane oxygenation 73 minutes after collapse. Ventricular tachyarrhythmias alternating with pulseless electrical activity resolved after eight hours. Following complete cardiac and neurological recovery, only adenoviral genome was found in myocardial biopsy. After 11 months, another episode of identical arrhythmias was rescued by an implantable cardioverter-defibrillator. CONCLUSION: Adequate prehospital and early hospital logistics is a prerequisite for successfully implementing extracorporeal cardiopulmonary resuscitation for refractory OHCA.

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)

Effect of Pulsatility on Microcirculation in Patients Treated with Extracorporeal Cardiopulmonary Resuscitation: A Pilot Study.

The effect of pulsatile blood flow on microcirculation during extracorporeal cardiopulmonary resuscitation (ECPR) is not elucidated; therefore, we designed an observational study comparing sublingual microcirculation in patients with refractory cardiac arrest (CA) with spontaneously pulsatile or low/nonpulsatile blood flow after treatment with ECPR. Microcirculation was assessed with Sidestream Dark Field technology in 12 patients with CA who were treated with ECPR and 12 healthy control subjects. Microcirculatory images were analyzed offline in a blinded fashion, and consensual parameters were determined for the vessels ≤20 µm. The patients' data, including actual hemodynamic parameters, were documented. Pulsatile blood flow was defined by a pulse pressure (PP) ≥ 15 mm Hg. Compared with the healthy volunteers, the patients who were treated with ECPR exhibited a significantly lower proportion of perfused capillaries (PPC); other microcirculatory parameters did not differ. The groups of patients with pulsatile (n = 7) versus low/nonpulsatile (n = 5) blood flow did not differ in regards to the collected data and hemodynamic variables (except for the PP and ejection fraction of the left ventricle) as well as microcirculatory parameters. In conclusion, microcirculation appeared to be effectively supported by ECPR in our group of patients with CA with the exception of the PPC. We found only nonsignificant contribution of spontaneous pulsatility to extracorporeal membrane oxygenation-generated microcirculatory blood flow.

Pathologic Intimal Thickening Plaque Phenotype: Not as Innocent as Previously Thought. A Serial 3D Intravascular Ultrasound Virtual Histology Study.

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 80mg and ezetimibe 10mg) with serial intravascular ultrasound imaging of nonculprit 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) (â¿¿15.14 ± 52.2; P = .001). The PIT was the most likely of all nonthin 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.

Non-invasive endothelial function assessment using digital reactive hyperaemia correlates with three-dimensional intravascular ultrasound and virtual histology-derived plaque volume and plaque phenotype.

BACKGROUND AND AIM: To study relationships between endothelial dysfunction (ED) and coronary atherosclerosis derived from intravascular ultrasound (IVUS) and virtual histology (VH). METHODS: Endothelial dysfunction was examined by EndoPAT system (Itamar Medical) in 56 patients who underwent IVUS and VH (Volcano corp.). Reactive hyperaemia index (RHI) < 2 was used for definition of ED. IVUS sequences were divided into 5 mm-long non-overlapping and adjacent vessel segments. Plaque phenotype was determined for each frame and 5 mm vessel segment was labeled according to highest frame score (from 0 for "no lesion" to 5 for "thin cap fibroatheroma; TCFA"). RESULTS: IVUS-VH data were collected from 41 patients suitable for three-dimensional analysis. Patients with ED exhibited larger plaque burden than those without ED (0.46 ± 0.08 vs. 0.39 ± 0.07, p = 0.014), smaller lumen area (8.59 ± 2.19 vs. 11.90 ± 3.50, p = 0.016), higher plaque risk score (2.82 ± 1.18 vs. 1.84 ± 0.90, p = 0.012), and higher number of TCFA frames (0.36 ± 0.22 vs. 0.22 ± 0.16, p = 0.038). Relative amounts of fibrous tissue correlated positively with RHI (p = 0.034, r = 0.33). The numbers of fibroatheromas and calcified plaques correlated with RHI inversely (r = -0.34, p = 0.031 and r = -0.32, p = 0.044, respectively). CONCLUSIONS: Endothelial dysfunction correlates with severity and phenotype of coronary lesions and can contribute to non-invasive detection of individuals with higher risk of cardiovascular events.

[Non-cardiogenic pulmonary edema, acute respiratory distress syndrome]. / Nekardiální plicní edém, syndrom akutní dechové tísne.

Non-cardiogenic pulmonary edema is a clinical syndrome manifested by rapidly progressive respiratory distress leading, without therapy, to severe respiratory insufficiency and subsequent multiorgan failure. The pathophysiological causes are: the change in the pressure gradients in the pulmonary capillaries, the impaired membrane permeability of the alveolocapillary in the lungs, and impaired lymphatic drainage. Unlike in cardiogenic pulmonary edema, cardiac disease is not a cause, and there is no increase in wedge pressure (< 18 mm Hg). The aetiological base is diverse and includes more clinical pathological factors. The diagnosis and evaluation are usually very difficult due to the rapidly deteriorating clinical condition of the patients. A decisive, quick and comprehensive approach, using all available invasive and non-invasive methods is necessary. The basic steps of treatment are: the use of different types of ventilatory support in order to achieve adequate oxygenation, dealing with possible hemodynamic instability, and, when needed, other specific procedures. It is always important to keep in mind that this is a very serious condition with a high mortality rate. And there is a need for fast and efficient access to the best specialized clinic.

The prediction of coronary artery disease based on non-invasive examinations and heme oxygenase 1 polymorphism versus virtual histology.

OBJECTIVE: Prediction of coronary atherosclerosis in patients with stable angina based on non-invasive examinations. METHODS: Pro-inflammatory markers, heme oxygenase-1 (HO-1) polymorphism, lipid levels, Framingham risk score (FRS), and carotid ultrasound were analyzed and compared to grayscale and virtual histology intravascular ultrasound (VH-IVUS). RESULTS: A total of 101 patients were included, and genetic analysis was performed on 81 patients (80.2%). The HO-1 risk polymorphism was more frequent in patients post-myocardial infarction (61.3% vs 32%; P=.0097), or with diabetes (68.4% vs 35.5%; P=.011) or a higher FRS (21.5 vs 15.7; P=.014). Plaques in patients with the HO-1 risk polymorphism contained less fibro-fatty tissue (17.1% vs 23.2%; P=.005) and more necrotic core (NC; 17.1% vs 12.7%; P=.02) and calcification (10.2% vs 5.7%; P=.035) compared to patients without the HO-1 risk polymorphism. Carotid intima media thickness (P=.05) and carotid bulb plaque (P=.008) predicted plaque burden. The level of Apo A inversely correlated with NC (P=.047; r = -0.27) and was lower in patients with VH-thin-cap fibroatheroma (VH-TCFA; 1.19 mmol/L vs 1.3 mmol/L; P=.04). FRS correlated with NC (P=.007; r = 0.2), with angiographic disease severity (P=.032; r = 0.21) and was higher in patients with VH-TCFA (9.1 vs 7.8; P=.03). CONCLUSION: Carotid ultrasound and HO-1 polymorphism improve coronary atherosclerosis prediction.

Virtual histology evaluation of atherosclerosis regression during atorvastatin and ezetimibe administration: HEAVEN study.

BACKGROUND: There is no study focusing on changes in coronary atherosclerosis during dual lipid-lowering therapy with statin and ezetimibe. METHODS AND RESULTS: Eighty-nine patients with stable angina randomized in a 1:1 ratio to Group A (aggressive therapy: atorvastatin 80mg, ezetimibe 10mg) and Group S (standard therapy) were analyzed. Treatment period was 12 months. Coronary arteries were examined by intravascular ultrasound and virtual histology. We found a decrease in the percent atheroma volume (PAV) (-0.4%) in Group A compared with an increase (+1.4%) in Group S (P=0.014) and this was accompanied by an increased frequency of combined atherosclerosis regression (increased lumen volume+decreased PAV) in group A (40.5%) compared with group S (14.9%) (P=0.007). The target low-density lipoprotein cholesterol level <2mmol/L, presence of at least 4 of 5 atherosclerotic risk factors, and decreased level of vascular cellular adhesive molecule were independent predictors of plaque regression. There were no significant differences in plaque composition between the 2 groups over the study duration. However, during analysis of the 2 groups together, fibrous and fibro-fatty tissues decreased and dense calcification and necrotic core increased during follow-up. CONCLUSIONS: Dual lipid-lowering therapy starts atherosclerosis regression, but does not lead to significant changes in plaque composition. The continuous shift in plaque from fibro and fibro-fatty to necrotic with calcification was present in both groups.

Lack of an association between connexin-37, stromelysin-1, plasminogen activator-inhibitor type 1 and lymphotoxin-alpha genes and acute coronary syndrome in Czech Caucasians.

BACKGROUND: The majority of acute coronary syndrome (ACS) cases cannot be explained by the analysis of commonly recognized risk factors; thus, the analysis of possible genetic predispositions is of interest. The genes for connexin-37, stromelysin-1, plasminogen activator-inhibitor type 1 (PAI-1) and lymphotoxin-alpha are among many presently known candidate genes that are associated with risk factors for ACS. OBJECTIVE: To identify the potential impact of the functional variants of connexin-37, stromelysin-1, PAI-1 and lymphotoxin-alpha on ACS in a Caucasian Czech population. METHODS: A total of 1399 consecutive patients (1016 men and 383 women) with ACS from five coronary care units located in Prague (Czech Republic) were analyzed; a representative sample of 2559 healthy individuals (1191 men and 1368 women) were also genotyped and served as controls. RESULTS: The gene variants analyzed were not significantly associated with the prevalence of ACS or the classical risk factors of ACS development such as high plasma lipid levels, hypertension, diabetes, high body mass index or smoking. CONCLUSION: In a Caucasian Czech population sample, genetic variants of connexin-37, stromelysin-1, PAI-1 and lymphotoxin-alpha were not significantly associated with a predisposition toward ACS.

A FTO variant and risk of acute coronary syndrome.

BACKGROUND: The FTO gene plays an important role in the determination of body weight and BMI and it has been suspected of being associated with all-case mortality. METHODS: We have analyzed the FTO rs17817449 variant in consecutive 1092 male patients with acute coronary syndrome (ACS) and in 1191 randomly selected Caucasian individuals (population controls). RESULTS: The FTO variant was significantly associated with BMI both in controls (P<0.02) and ACS patients (P<0.01). In both groups, BMI was highest in GG homozygotes and lowest in TT homozygotes. There was a significant difference between the ACS patients and controls in the frequency of the FTO genotype GG (21.4% vs. 15.9%, P<0.005). FTO GG homozygotes had a significantly increased risk of ACS, compared with TT homozygotes which was independent of age and BMI (odds ratio 1.49, 95% confidence interval 1.16-1.93). The odds ratio of ACS patients for the GG genotype remained significant even after the exclusion of diabetics (100 controls and 339 ACS patients), with OR 1.32 (95% CI 1.01-1.72). CONCLUSIONS: This study provides an evidence of an association between the FTO variant and risk of ACS in Caucasian males.

Variability of aortic blood flow predicts fluid responsiveness in spontaneously breathing healthy volunteers.

BACKGROUND: Assessment of fluid responsiveness is an important topic in acute cardiology. Echocardiographic measurement of respiratory variations of aortic blood velocity in ventilated shock patients can accurately predict the effect of volume expansion. On the other hand, it remains unclear whether this respiratory variability is a common physiological reaction to hypovolaemia and whether its measurement is applicable also in spontaneously breathing patients. AIM: To assess whether respiratory variability of peak aortic blood flow velocity (DVpeakao) and of aortic velocity time integral (DVTIao) reflects preload-dependent changes of cardiac index (CI) and whether it predicts fluid responsiveness in healthy spontaneously breathing volunteers. METHODS: DVpeakao, DVTIao and CI were measured by transthoracic echocardiography in 20 volunteers at baseline and after intravenous administration of furosemide (0.5 mg/kg). Afterwards, volunteers were randomised to rapid intravenous volume expansion (group A) or no expansion (group B) and assessed finally. RESULTS: Hypovolaemia induction was associated with a decrease of CI (from 3.25 +/- 0.50 to 2.28 +/- 0.43 l/min/m2, p < 0.001) which correlated with an increase of DVpeakao (r = -0.490, p = 0.028) and DVTIao (r = -0.554, p = 0.011) in both groups. In group A, volume expansion was followed by a drop of DVpeakao (from 16.04 +/- 1.99 to 2.97 +/- 1.65 %, p < 0.001) and DVTIao (from 20.43 +/- 5.13 to 3.43 +/- 1.68 %, p < 0.001) and CI increase (from 2.14 +/- 0.47 to 3.29 +/- 0.57 l/min/m2, p < 0.001). This increase strongly correlated with the value of DVpeakao (r = 0.782, p = 0.008) and DVTIao (r = 0.770, p = 0.009) before volume expansion. Conversely, there was no change of measured parameters in group B. Threshold values of 14% for DVaopeak and 17% for DVTIao were identified to predict fluid responsiveness (increase of CI > 15%) with a sensitivity of 89% and specificity of 100%. CONCLUSIONS: DVpeakao and DVTIao reflect preload-dependent changes of CI in healthy spontaneously breathing volunteers and predict fluid responsiveness.

Clopidogrel pre-treatment in stable angina: for all patients > 6 h before elective coronary angiography or only for angiographically selected patients a few minutes before PCI? A randomized multicentre trial PRAGUE-8.

AIMS: To compare two different clopidogrel regimens on the outcomes of patients undergoing elective coronary angiography (CAG)+/-ad hoc percutaneous coronary intervention (PCI). METHODS AND RESULTS: Open-trial randomized 1028 patients with stable angina to group A ('non-selective'-clopidogrel 600 mg > 6 h before CAG; n = 513) or group B ('selective'-clopidogrel 600 mg in the cath-lab after CAG, only in case of PCI; n = 515). Combined primary endpoint was death/periprocedural myocardial infarction (MI)/stroke/re-intervention within 7 days. Secondary endpoints were troponin elevation and bleeding complications. Primary endpoint occurred in 0.8% group A patients vs. 1% group B (P = 0.749; 90% CI for the percentage difference -1.2-0.8). Periprocedural troponin elevation (> 3 x ULN) was detected in 2.6% group A vs. 3.3% group B (P = 0.475; 90% CI -2.5-1.0). Bleeding complications occurred in 3.5% group A patients vs. 1.4% group B (P = 0.025). After adjustment for covariates and factors that may influence the bleeding risk, patients in group A were shown to have more likely bleeding complications when compared with group B (OR = 3.03; 95% CI 1.14-8.10; P = 0.027). CONCLUSION: High (600 mg) loading dose of clopidogrel before elective CAG increased the risk of minor bleeding complications, while the benefit on periprocedural infarction was not significant. Clopidogrel can be given safely in the catheterization laboratory between CAG and PCI in chronic stable angina patients.