Extracorporeal cardiopulmonary resuscitation-based approach to refractory out-of-hospital cardiac arrest: A focus on organ donation, a secondary analysis of a Prague OHCA randomized study.

BACKGROUND: Refractory out-of-hospital cardiac arrest (OHCA) has a poor outcome. In patients, who cannot be rescued despite using advanced techniques like extracorporeal cardiopulmonary resuscitation (ECPR), organ donation may be considered. This study aims to evaluate, in refractory OHCA, how ECPR versus a standard-based approach allows organ donorship. METHODS: The Prague OHCA trial randomized adults with a witnessed refractory OHCA of presumed cardiac origin to either an ECPR-based or standard approach. Patients who died of brain death or those who died of primary circulatory reasons and were not candidates for cardiac transplantation or durable ventricle assist device were evaluated as potential organ donors by a transplant center. In this post-hoc analysis, the effect on organ donation rates and one-year organ survival in recipients was examined. RESULTS: Out of 256 enrolled patients, 75 (29%) died prehospitally or within 1 hour after admission and 107 (42%) during the hospital stay. From a total of 24 considered donors, 21 and 3 (p = 0.01) were recruited from the ECPR vs standard approach arm, respectively. Fifteen brain-dead and none cardiac-dead subjects were ultimately accepted, 13 from the ECPR and two from the standard strategy group. A total of 36 organs were harvested. The organs were successfully transplanted into 34 recipients. All transplanted organs were fully functional, and none of the recipients died due to graft failure within the one-year period post-transplant. CONCLUSION: The ECPR-based approach in the refractory OHCA trial is associated with increased organ donorship and an excellent outcome of transplanted organs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01511666. Registered January 19, 2012.

The impact of atrial fibrillation and atrial tachycardias on the hemodynamic status of patients with pulmonary hypertension.

The impact of atrial fibrillation and atrial tachycardias (AF/AT), and their optimal treatment strategy in PH patients is still being discussed. The goal of this study was to evaluate the effect of AF/AT termination on the hemodynamic parameters in PH patients. We compared patients with pre-capillary pulmonary hypertension (PH group), left ventricular heart failure (LV-HF group), and a Control group. A repeated right heart catheterization was performed during the catheter ablation (CA) procedure. The first measurement was done in arrhythmia, the second after the sinus rhythm (SR) was restored. High frequency atrial stimulation was used to simulate AT in patients without arrhythmia presence at the time of the CA. The variation of pressure parameters in PH patients did not differ significantly from the Controls. There was a significant increase in the right ventricle pressure after the SR restoration in the LV-HF group compared to the Controls and PH group (+4 vs. -2 vs. -3 mmHg, p<0.05). The cardiac index (CI) variation was not significant when compared between the study groups. An increase of the CI after the SR restoration was found in those patients with AF (+0.31 l/min/m2 [IQR 0.18; 0.58]) in contrast to those patients with organized AT/high frequency atrial stimulation ( 0.09 l/min/m2, [IQR - 0.45; 0.19]). This difference was statistically significant (p<0.05). The acute hemodynamic response to arrhythmia termination was not significantly different in the PH patients when compared to the Controls. In contrast to AT/high frequency stimulation, the restoration of SR in AF patients leads to an increased CI, irrespective of the presence or absence of PH.

The Role of Pulmonary Artery Wedge Pressure on the Incidence of Atrial Fibrillation and Atrial Tachycardias in Patients With Isolated Pre-capillary Pulmonary Hypertension.

Atrial fibrillation and atrial tachycardias (AF/AT) have been reported as a common condition in patients with pulmonary hypertension (PH). As yet, limited data exists about the significance of the borderline post-capillary pressure component on the occurrence of AF / AT in patients with isolated pre-capillary PH. We retrospectively studied the prevalence of AF / AT in 333 patients (mean age 61 ± 15 years, 44% males) with pre-capillary idiopathic / familiar pulmonary arterial hypertension, and inoperable chronic thromboembolic pulmonary hypertension. The prevalence of AF / AT was analyzed in different categories of pulmonary artery wedge pressure (PAWP). In the study population overall, the mean PAWP was 10.5 ± 3 mmHg, median of 11 mmHg, range 2-15 mmHg. AF / AT was diagnosed in 79 patients (24%). The proportion of AF / AT among patients with PAWP below the median (?11 mmHg) was lower than in subjects with PAWP between 12 and 15 mmHg, 30 (16%) vs. 46 (35%), p = 0.0001. Compared to the patients with PAWP?11 mmHg, subjects with PAWP between 12 and 15 mmHg were older (65 ± 13 years vs. 58 ± 16), with more prevalent arterial hyperte\nsion [100 (70%) vs. 106 (55%)] and diabetes mellitus [50 (35%) vs. 48 (25%)], showed larger size of the left atrium (42 ± 7 vs. 40 ± 6 mm), and higher values of right atrium pressure (12 ± 5 vs. 8 ± 5 mm Hg), p < 0.05 in all comparisons. The prevalence of AF / AT in the group studied increased with the growing post-capillary component.

Disparity between two-dimensional echocardiographic and electroanatomic left and right atrial volumes in patients undergoing catheter ablation for long-standing persistent atrial fibrillation.

Left atrial (LA) volume (LAV) is used for the selection of patients with atrial fibrillation (AF) to rhythm control strategies. Calculation of LAV from the LA diameters and areas by two-dimensional (2D) echocardiography may result in significant error. Accuracy of atrial volume assessment has never been studied in patients with long-standing persistent AF (LSPAF) and significant atrial remodeling. This study investigated correlation and agreement between 2D echocardiographic (Simpson method) and electroanatomic (CARTO, Biosense Webster) left and right atrial (RA) volumes (LAV(ECHO) vs. LAV(CARTO) and RAV(ECHO) vs. RAV(CARTO)) in patients undergoing catheter ablation for LSPAF. The study enrolled 173 consecutive subjects (females: 21 %, age: 59+/-9 years). There was only modest correlation between LAV(ECHO) (92+/-31 ml) and LAV(CARTO) (178+/-37 ml) (R=0.57), and RAV(ECHO) (71+/-29 ml) and RAV(CARTO) (173+/-34 ml) (R=0.42), respectively. LAV(ECHO) and RAV(ECHO) underestimated LAV(CARTO) and RAV(CARTO) with the absolute bias (+/-1.96 standard deviation) of -85 (-148; -22) ml and -102 (-169; -35) ml, respectively, and with the relative bias of -48 (-75; -21) % and -59 (-88; -30) %, respectively (all P<0.000001 for their mutual difference). Significant confounders of this difference were not identified. In patients with LSPAF, 2D echocardiography significantly underestimated both LA and RA volumes as compared with electroanatomic reference. This disagreement was independent of clinical, echocardiographic and mapping characteristics.

Arterial stiffening contributes to impairment of cerebrovascular reactivity in patients with coronary artery disease without carotid stenosis.

Impaired cerebrovascular reactivity (CVR), an important risk factor for future stroke, is affected by a presence carotid stenosis. However, in some cases CVR can be impaired in the absence of carotid stenosis due to several poorly characterized mechanisms. We hypothesized that arterial stiffening as observed in coronary heart disease (CHD) could be associated with alteration in CVR in CHD patients without carotid stenosis. The study population consisted of patients referred for coronary angiography without significant carotid stenosis (<50 %). CVR was evaluated by breath holding index (BHI) measured with transcranial color code duplex ultrasound. Arterial stiffness was assessed by pulse wave velocity (PWV) measured by the oscillometric method. The extent of coronary atherosclerosis was quantified by Gensini score (GS). Out of 186 subjects, sixty-two patients fulfilled the inclusion and exclusion criteria. BHI decreased with increasing PWV (r = -0.47, p<0.001). Decrease in BHI was significantly inversely associated with GS (r = -0.61, p<0.001). GS was associated with PWV (p<0.001). In conclusion, impaired CVR was associated with increased arterial stiffening in CHD patients in the absence of significant carotid stenosis. Thus, we speculate that increased arterial stiffness may at least partially contribute to the pathophysiology of CVR alteration in coronary artery disease.

Are there any differences between stress hormone levels in non-stress conditions and in potentional stress overload (heart catheterisation) in sows?

In order to study a possible effect of mini-invasive heart intervention on a response of hypothalamo-pituitary-adrenal stress axis, we analyzed four stress markers (cortisol, cortisone, DHEA and DHEAS) in 25 sows using minimally invasive heart catheterisation as the stress factor. The marker levels were assessed in four periods of the experiment, (1) the baseline level on the day before intervention, (2) after the introduction of anesthesia, (3) after conducting tissue stimulation or ablation, and (4) after the end of the catheterisation. For statistical analyses we used the non-parametric Friedman test for four dependent samples (including all four stages of the operation) or three dependent samples (influence of operation only, baseline level was excluded). Statistically significant differences in both Friedman tests were found for cortisol and for cortisone. Significant differences for DHEA as well as for DHEAS were found for all tested stages but not for the effect of operation itself. We have concluded that cortisol levels are blunted by the influence of anesthesia after its administration, and therefore decrease back to the baseline at the end of the operation. The other markers (cortisone, DHEA and DHEAS) acted as balanced systems against the injurious stress effect.

Hemodynamic and metabolic parameters during prolonged cardiac arrest and reperfusion by extracorporeal circulation.

Extracorporeal membranous oxygenation (ECMO) is increasingly used in the management of refractory cardiac arrest. Our aim was to investigate early effects of ECMO after prolonged cardiac arrest. In fully anesthetized swine (48 kg, N=18) ventricular fibrillation (VF) was induced and untreated period (20 min) of cardiac arrest commenced, followed by 60 min extracorporeal reperfusion (ECMO flow 100 ml/kg.min). Hemodynamics, arterial blood gasses, plasma potassium, tissue oximetry (StO(2)) and cardiac (EGM) and cerebral (BIS) electrophysiological parameters were continuously recorded and analyzed. Within 3 minutes of VF hemodynamic and oximetry parameters fall abruptly while metabolic parameters destabilize gradually over 20 minutes peaking at pH 7.04 ± 0.05, pCO(2) 89 ± 14 mmHg, K(+) 8.5 ± 1.6 mmol/l. During reperfusion most parameters restore rapidly: within 3-5 minutes mean arterial pressure reaches >40 mmHg, StO(2)>50 %, paO(2)>100 mmHg, pCO(2)<50 mmHg, K(+)<5 mmol/l. EGMs mean amplitude peaks at 4.5 ± 2.4 min. Cerebral activity (BIS>60) reappeared in 5 animals after 87 ± 21 min. In 12/18 animals return of spontaneous circulation was achieved. In conclusions, ECMO provides rapid restitution of internal milieu even after prolonged arrest. However, despite normalization of global parameters full recovery was not guaranteed since cardiac and cerebral electrical activities were sufficiently restored only in some animals. More sensitive and organ specific indicators need to be identified in order to estimate adequacy of cardiac support devices.

Distribution of mean cycle length in cavo-tricuspid isthmus dependent atrial flutter.

Although cycle length (CL) constitutes a fundamental descriptor of any arrhythmia, there is not larger study describing mean CL in electrophysiologically confirmed cavo-tricuspid isthmus (CTI)-dependent atrial flutter (AFL). We analyzed retrospectively digital recordings of 121 patients (98 men; age 64+/-11 years) referred for radiofrequency ablation of persistent CTI-dependent AFL. Median of mean AFL CL was 240 ms (interquartile range (IQR) of 222-258 ms, overall range of 178-399 ms). The distribution of CL was not normal (Shapiro Wilk test, p<0.001). Both counterclockwise and clockwise (14.9 % of all cases) AFLs were comparable in their CL; 240 (IQR 222-258) ms vs. 234 (217-253) ms, respectively. AFL CL<200 ms and AFL CL<190 ms was noticed in 5 (4.1 %) and 3 cases (2.5 %), respectively. In multivariate regression analysis, age (increase by 6+/-3 ms per decade of age, p=0.036), treatment with specific antiarrhythmic drugs (increase by 11+/-6 ms, p=0.052) and the history of cardiac surgery (increase by 26+/-9 ms, p=0.004) were independently associated with AFL CL. In conclusions, the distribution of AFL CL is not normal. The prevalence of AFL with short CL is low. Short CL<200 ms does not rule out the CTI-dependent AFL, especially in young and otherwise healthy patients.

Might cardiac catheterization influence diurnal rhythm of the steroid stress hormones secretion?

Glucocorticoids (GCs) are steroid hormones produced by the adrenal cortex in reaction to stress stimuli. GCs production is not stable over a 24-hour period; the plasma concentration peaks in the morning (approximately upon awakening) and then the plasma levels decrease, reaching the nadir in the evening. In our experiments, the levels of cortisol, cortisone, DHEA and DHEAS were tested in young female pigs (n=23) during heart catheterization at two different day times (in the morning and in the afternoon). The non-parametric Mann-Whitney test for statistical analysis was used. We found only minimal statistical differences in studied markers between the morning and afternoon group (p>0.05). The absence of circadian variation in GCs levels could originate either at an early age of our experimental pigs, or in stressful conditions on the experiment day, or most likely the day before (e.g. social isolation, fasting, transport, and catheterization), respectively. We can conclude there is no difference in the stress load between morning and afternoon experiments, and therefore we can assume the stress load is not a limiting factor for the timing when catheterization should be preferably performed.

Is there circadian variation in cortisol levels in young sows in heart catheterization?

Cortisol is the main glucocorticoid (GC) hormone in pigs associated with stress response. It is well known that GCs levels are not stable during the day; their concentration is a circadian variable with the peak in the morning and the nadir in the night (in diurnal animals). Circadian variation is present during postnatal ontogeny. The onset of the circadian fluctuation occurs in pigs at the age of 3 to 20 weeks (according to the literature). The aim of our pilot study was to determine if young sows (used in cardiosurgical experiments) already developed the circadian variation. Twelve-week-old sows were used in the heart catheterization experiment. Cortisol was measured during four different stages of the experiment at two different times of the day (the operation was performed in the morning or afternoon). To determine circadian variation the Mann-Whitney test was used; to determine changes in cortisol levels within the experiment the Friedman test was performed. We didn't find any circadian variation (p>0.05) or statistical significant variation in the Friedman test (p>0.05). We assumed that our pigs are too young to have circadian rhythm present. Our findings are in accordance with many authors.

[Improvement of quality of life after ablation of longstanding persistent versus paroxysmal atrial fibrillation: results of 2-year follow-up]. / Zlepsení kvality zivota po ablaci dlouhodobe perzistentní versus paroxysmální fibrilace síní: výsledky dvouletého sledování.

AIMS: The purpose of the study was to assess quality of life and socio-economic parameters in patients after ablation of paroxysmal versus longstanding persistent atrial fibrillation (AF). METHODS: The study included 89 patients with paroxysmal AF and 56 patients with longstanding persistent AF who underwent ablation within 1 year, and were afterwards prospectively followed up for 2 years. Quality of life was evaluated by the EQ-5D questionnaire before and every 6 months after ablation. RESULTS: Objective, respectively subjective quality of life at baseline was lower in patients with longstanding persistent AF (67 +/- 16 vs 71 +/- 10; p = 0.01, resp. 64 +/- 12 vs 67 +/- 16; p = 0.07); however, after 2 years, it exceeded that of the patients with paroxysmal AF (80 +/- 17 vs 75 +/- 18; p = 0.03; resp. 73 +/- 13 vs 70 +/- 17; p = 0.18). The baseline-2 year difference in improvement was higher in patients with longstanding persistent AF in both objective (p = 0.001) and subjective component (p = 0.05). Both groups displayed significant decrease in the days of hospitalization, and the days of working incapacity. CONCLUSION: Patients with longstanding persistent AF exhibit worse baseline quality of life than the patients with paroxysmal AF, and higher quality of life improvement after ablation.

QT dispersion estimated from 80 body surface potential map leads and from standard 12-leads ECG in psychiatric patients treated with dosulepin.

The aim of the study was to detect changes of the QT dispersion (QTd) due to cardiotoxicity of tricyclic antidepressant dosulepin. Electrocardiographic and body surface potential mapping (BSPM) recordings were obtained using Cardiag 112.2 diagnostic system from 27 psychiatric outpatients treated with prophylactic doses of dosulepin and compared to those obtained from 37 healthy volunteers. From these recordings the QTd and the dispersion of heart rate-corrected QT interval QTc were evaluated. These parameters were estimated both from 80 BSPM leads and from 12 standard ECG leads. Acquired data were statistically correlated by Spearman rank order correlation coefficient with dosulepin plasma levels. The average QTd evaluated from BSPM leads (+/-SD) in the dosulepin group was significantly higher [70 (+/-21) ms] than that in the control group [34 (+/-12) ms] (P< 0.001). Moreover, the correlation between QTd and the dosulepin plasma level was statistically significant as well (P< 0.001) with the value of correlation coefficient 0.7871. The QTd evaluated from standard 12 ECG leads was increased in dosulepin group as well [46 (+/-18) ms vs. 28 (+/-10) ms - P< 0.05] but we have not found any significant correlation of the QTd with the dosulepin plasma level. According to the above-mentioned results we can conclude that the QTd estimated from BSPM leads (but not that estimated from 12-lead ECG) could be used as a marker of the dosulepin effect on the myocardium.

QT dispersion and electrical heart field morphology in patients treated with dosulepin.

The aim of the study was to detect the changes of QT dispersion (QTd) due to cardiotoxicity of tricyclic antidepressant dosulepin. Electrocardiographic and vectorcardiographic recordings were obtained using Cardiag 112.2 diagnostic system from 28 psychiatric outpatients treated with prophylactic doses of dosulepin and compared to those obtained from 37 healthy volunteers. From these recordings following parameters were evaluated: QTd, spatial QRS-STT angle and amplitude of T-wave. The acquired data were correlated with the dosulepin plasma levels using Spearman's rank order correlation test. The average QTd (+/-S.D.) in the dosulepin group was significantly higher (70+/-21 ms) than that in the control group (34+/-12 ms) (P<0.001). Moreover, the correlation between QTd and the dosulepin plasma levels was highly significant (r = 0.7871, P<0.001). Similar results were obtained when QTc dispersion was used. On the contrary, the QRS-STT space angle did not correlate with the dosulepin plasma levels. Furthermore, the T-wave amplitude was not significantly correlated to the QT-interval. Thus we can conclude that the QT dispersion could be used as a simple marker of the dosulepin effect on the myocardium.

QT dispersion and T-loop morphology in late pregnancy and after delivery.

The aim of the study was to detect changes of both the QT dispersion and T-loop morphology resulting from the changed spatial position of the heart during pregnancy. Electrocardiographic and vectorcardiographic recordings were obtained from 37 healthy women 19-36 years old in the 36th to 40th week of physiological pregnancy and 2 to 6 days after delivery. The same recordings were obtained from 18 healthy women of the same age. The average QT dispersion (+/- S.D.) in normal subjects was significantly lower (34 +/- 12 ms) than in those in late pregnancy (73 +/- 18 ms) (P < 0.001). The average amplitude of T-loop (Ta) in women in late pregnancy was significantly (P < 0.001) smaller (532 +/- 98 microV) and the width of T-loop (Tw) was wider (21.24 +/- 11.48 deg) than in the control group (793 +/- 114 microV and 7.17 +/- 3.02 deg, respectively). The partial post-partum restoration of all parameters was not significant. In all groups, the QT dispersion was significantly correlated with Tw but not with Ta. According to these results we can conclude that the QT dispersion is an indirect reflection of the complete process of ventricular repolarization, reflected in the morphology of the T-loop.