Hypertriglyceridemia and omega-3 fatty acids: Their often overlooked role in cardiovascular disease prevention.

AIMS: This review aims to describe the pathogenic role of triglycerides in cardiometabolic risk, and the potential role of omega-3 fatty acids in the management of hypertriglyceridemia and cardiovascular disease. DATA SYNTHESIS: In epidemiological studies, hypertriglyceridemia correlates with an increased risk of cardiovascular disease, even after adjustment for low density lipoprotein cholesterol (LDL-C) levels. This has been further supported by Mendelian randomization studies where triglyceride-raising common single nucleotide polymorphisms confer an increased risk of developing cardiovascular disease. Although guidelines vary in their definition of hypertriglyceridemia, they consistently define a normal triglyceride level as <150 mg/dL (or <1.7 mmol/L). For patients with moderately elevated triglyceride levels, LDL-C remains the primary target for treatment in both European and US guidelines. However, since any triglyceride level in excess of normal increases the risk of cardiovascular disease, even in patients with optimally managed LDL-C levels, triglycerides are an important secondary target in both assessment and treatment. Dietary changes are a key element of first-line lifestyle intervention, but pharmacological treatment including omega-3 fatty acids may be indicated in people with persistently high triglyceride levels. Moreover, in patients with pre-existing cardiovascular disease, omega-3 supplements significantly reduce the risk of sudden death, cardiac death and myocardial infarction and are generally well tolerated. CONCLUSIONS: Targeting resistant hypertriglyceridemia should be considered as a part of clinical management of cardiovascular risk. Omega-3 fatty acids may represent a valuable resource to this aim.

Cerebral hemodynamics during atrial fibrillation: Computational fluid dynamics analysis of lenticulostriate arteries using 7 T high-resolution magnetic resonance imaging.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, inducing irregular and faster heart beating. Aside from disabling symptoms-such as palpitations, chest discomfort, and reduced exercise capacity-there is growing evidence that AF increases the risk of dementia and cognitive decline, even in the absence of clinical strokes. Among the possible mechanisms, the alteration of deep cerebral hemodynamics during AF is one of the most fascinating and least investigated hypotheses. Lenticulostriate arteries (LSAs)-small perforating arteries perpendicularly departing from the anterior and middle cerebral arteries and supplying blood flow to basal ganglia-are especially involved in silent strokes and cerebral small vessel diseases, which are considered among the main vascular drivers of dementia. We propose for the first time a computational fluid dynamics analysis to investigate the AF effects on the LSAs hemodynamics by using 7 T high-resolution magnetic resonance imaging (MRI). We explored different heart rates (HRs)-from 50 to 130 bpm-in sinus rhythm and AF, exploiting MRI data from a healthy young male and internal carotid artery data from validated 0D cardiovascular-cerebral modeling as inflow condition. Our results reveal that AF induces a marked reduction of wall shear stress and flow velocity fields. This study suggests that AF at higher HR leads to a more hazardous hemodynamic scenario by increasing the atheromatosis and thrombogenesis risks in the LSAs region.

Long-term (≥15 years) Follow-up of Percutaneous Coronary Intervention of Unprotected Left Main (From the GRAVITY Registry).

Long term survival and its determinants after Percutaneous Coronary Intervention (PCI) on Unprotected Left Main Coronary Artery (ULMCA) remain to be appraised. In 9 European Centers 470 consecutive patients performing PCI on ULMCA between 2002 and 2005 were retrospectively enrolled. Survival from all cause and cardiovascular (CV) death were the primary end points, while their predictors at multivariate analysis the secondary ones. Among the overall cohort 81.5% of patients were male and mean age was 66 ± 12 years. After 15 years (IQR 13 to 16), 223 patients (47%) died, 81 (17.2%) due to CV etiology. At multivariable analysis, older age (HR 1.06, 95%CI 1.02 to 1.11), LVEF < 35% (HR 2.97, 95%CI 1.24 to 7.15) and number of vessels treated during the index PCI (HR 1.75, 95%CI 1.12 to 2.72) were related to all-cause mortality, while only LVEF <35% (HR 4.71, 95%CI 1.90 to 11.66) to CV death. Repeated PCI on ULMCA occurred in 91 (28%) patients during the course of follow up and did not significantly impact on freedom from all-cause or CV mortality. In conclusion, in a large, unselected population treated with PCI on ULMCA, 47% died after 15 years, 17% due to CV causes. Age, number of vessels treated during index PCI and depressed LVEF increased risk of all cause death, while re-PCI on ULMCA did not impact survival.

Pdgf1aa regulates zebrafish neural crest cells migration through Hif-1 in an oxygen-independent manner.

The transcription factor Hif-1α regulates epithelial to mesenchymal transition and neural crest cell chemotaxis in Xenopus. Hif-1α is only stabilised under low oxygen levels, and the in vivo stabilisation of this factor in neural crest cells is poorly understood. Multiple oxygen-independent Hif-1α regulators have been described in cell cultures and cancer models. Among these, the PDGF pathway has been linked to neural crest development. The present study established a connection between the Pdgf pathway and Hif-1α stabilisation in zebrafish. Specifically, embryos with a disrupted Pdgf pathway were rescued by employing hif-1α mRNA through qPCR and immunohistochemistry techniques. The data suggest that oxygen levels in the neural crest are normal and that Pdgf1aa regulates neural crest migration through Hif-1α expression.

The ups and downs of Wnt signaling in prevalent neurological disorders.

In order to function properly, the brain must be wired correctly during critical periods in early development. Mistakes in this process are hypothesized to occur in disorders like autism and schizophrenia. Later in life, signaling pathways are essential in maintaining proper communication between neuronal and non-neuronal cells, and disrupting this balance may result in disorders like Alzheimer's disease. The Wnt/beta-catenin pathway has a well-established role in cancer. Here, we review recent evidence showing the involvement of Wnt/beta-catenin signaling in neurodevelopment as well as in neurodegenerative diseases. We suggest that the onset/development of such pathological conditions may involve the additive effect of genetic variation within Wnt signaling components and of molecules that modulate the activity of this signaling cascade.

Renal metabolism of amino acids and ammonia in subjects with normal renal function and in patients with chronic renal insufficiency.

The net renal metabolism of amino acids and ammonia in the post absorptive state was evaluated in subjects with normal renal function and in patients with chronic renal insufficiency by measuring renal uptake and release, and urinary excretion of free amino acids and ammonia. In normal subjects the kidney extracts glutamine, proline, citrulline, and phenylalanine and releases serine, arginine, taurine, threonine, tyrosine, ornithine, lysine, and perhaps alanine. The renal uptake of amino acids from arterial blood occurs by way of plasma only, whereas approximately a half of amino acid release takes place by way of blood cells. Glycine is taken up from arterial plasma, while similar amounts of this amino acid are released by way of blood cells. In the same subjects total renal ammonia production can be largely accounted for by glutamine extracted. In patients with chronic renal insufficiency (a) the renal uptake of phenylalanine and the release of taurine and ornithine disappear; (b) the uptake of glutamine and proline, and the release of serine and threonine are reduced by 80--90%; (c) the uptake of citrulline and the release of alanine, arginine, tyrosine, and lysine are reduced by 60--70%; (d) no exchange of glycine is detectable either by way of plasma or by way of blood cells; (e) exchange of any other amino acid via blood cells disappears, and (f) total renal ammonia production is reduced and not more than 35% of such production can be accounted for by glutamine extracted, so that alternative precursors must be used. A 140% excess of nitrogen release found in the same patients suggests an intrarenal protein and peptide breakdown, which eventually provides free amino acids for ammonia production.

Scopolamine increases vagal tone and vagal reflexes in patients after myocardial infarction.

OBJECTIVES: The goal of this study was to assess the hypothesis that transdermal scopolamine would increase vagal activity in patients after myocardial infarction. BACKGROUND: In postmyocardial infarction patients, low heart rate variability and reduced baroreceptor reflex sensitivity are associated with increased mortality. Accordingly, there is an increasing interest in a mechanism for shifting the sympathovagal balance toward vagal dominance. METHODS: The effects of transdermal administration of scopolamine on heart rate variability and baroreceptor reflex sensitivity were assessed in 20 patients (mean age 59 +/- 11 years) by pharmacologic washout 14 +/- 3 days after myocardial infarction. Heart rate variability and baroreceptor reflex sensitivity were measured 24 h after application of the scopolamine patch and compared with the values measured before scopolamine and after application of a placebo patch. The following variables were derived from a 15-min electrocardiographic recording: the mean RR interval and its standard deviation, the mean square successive difference, the percent of intervals differing > 50 ms from the preceding RR interval and the low and high frequency areas resulting from power spectral analysis. RESULTS: The placebo patch had no effect on the variables measured. Scopolamine increased both heart rate variability and baroreceptor reflex sensitivity significantly. Specifically, the mean RR interval and its standard deviation increased by 7.1% (p = 0.01) and 25% (p = 0.004), respectively. The mean square successive difference increased by 38% (p = 0.0003) and the percent of intervals differing > 50 ms from the preceding interval by 100% (p = 0.001). The ratio of low to high frequency areas of the power spectrum decreased by 24% (p = 0.02), and baroreceptor reflex sensitivity increased by 42% (p = 0.0006). These effects were also evident in patients with very low initial values. Side effects were minimal. CONCLUSIONS: Transdermal scopolamine increased measures of heart rate variability and baroreceptor reflex sensitivity in patients with a recent myocardial infarction toward values associated with a better prognosis. Pharmacologic modulation of the autonomic balance by scopolamine or related drugs deserves evaluation as a new and promising approach to reduce risk after myocardial infarction.

Pharmacologic modulation of the autonomic nervous system in the prevention of sudden cardiac death. A study with propranolol, methacholine and oxotremorine in conscious dogs with a healed myocardial infarction.

OBJECTIVES: The goal of the present study was to evaluate the antifibrillatory and hemodynamic effects of pharmacologic muscarinic activation and to compare them with those of beta-adrenergic blockade. BACKGROUND: Recent studies suggest a correlation between increased vagal activity and a reduced incidence of sudden cardiac death. Electrical stimulation of the vagus nerve reduces the incidence of ventricular fibrillation in a conscious animal model of sudden cardiac death. METHODS: Eleven dogs with healed anterior myocardial infarction, in which a 2-min left circumflex coronary artery occlusion during exercise caused ventricular fibrillation, were studied. They underwent subsequent tests with saline solution, propranolol (1 mg/kg body weight), methacholine (0.5 microgram/kg per min) and oxotremorine (8 micrograms/kg). RESULTS: In the test with saline solution, 100% of the dogs developed ventricular fibrillation; this occurred in only 10% of the tests with propranolol (95% confidence interval 0.2% to 44%; p < 0.001), 60% of the tests with methacholine (95% confidence interval 26% to 88%, p = 0.05) and 37.5% of the tests with oxotremorine (95% confidence interval 8% to 75%, p = 0.005). Propranolol and oxotremorine significantly reduced heart rate compared with saline solution, whereas methacholine did not. Propranolol significantly reduced maximal first derivative of left ventricular pressure, (dP/dtmax), particularly during myocardial ischemia, compared with the other treatments (2,391 +/- 582 mm Hg/s [mean +/- 1 SD] with propranolol vs. 4,226 +/- 1,237, 4,922 +/- 584 and 4,358 +/- 1,109 mm Hg/s with saline solution, methacholine and oxotremorine, respectively, p < 0.005). CONCLUSIONS: Propranolol was extremely effective against ventricular fibrillation. Methacholine and oxotremorine provided a significant, although less marked, protection and caused much less impairment of contractility compared with propranolol. Muscarinic receptor activation may represent a new approach to prevention of sudden cardiac death, particularly when beta-blockers are contraindicated and negative inotropic effects are to be avoided.

Impaired baroreflex sensitivity is correlated with hemodynamic deterioration of sustained ventricular tachycardia.

OBJECTIVES: The goal of this study was to evaluate clinical and autonomic variables (heart rate variability and baroreflex sensitivity) related to hemodynamic tolerability of VT in patients with sustained monomorphic VT and a healed myocardial infarction. BACKGROUND: Sustained ventricular tachycardia (VT) with hemodynamic deterioration is associated with a worse prognosis than that of well tolerated VT. The causes of hemodynamic deterioration of VT are incompletely understood. METHODS: Twenty-four consecutive patients with sustained monomorphic VT and a healed myocardial infarction (mean age +/- SD 66 +/- 8 years, left ventricular [LV] ejection fraction 37 +/- 11%) were assigned to group 1 if the VT was well tolerated (n = 11) or to group 2 if faintness or syncope occurred or if systolic blood pressure was < 90 mm Hg with clinical signs of shock (n = 13). RESULTS: No difference was found between the two groups in age, LV function, rate and duration of the VT or heart rate variability. However, patients in group 2 had a significantly lower baroreflex sensitivity (3.4 +/- 1.1 vs. 7.1 +/- 3.7 ms/mm Hg, p = 0.003). Multiple logistic regression analysis showed that only the value of baroreflex sensitivity (p = 0.0003)-but not age, LV ejection fraction, VT cycle length or SD of the RR interval (all p > 0.25)-correlated with the tolerability of the VT. Finally, LV ejection fraction (p = 0.0001) and baroreflex sensitivity (p = 0.0003)-but not age, cycle length of the tachycardia or SD of the RR interval-predicted cardiac death or unstable VT during follow-up. CONCLUSIONS: These data suggest that an impaired cardiovascular reflex response may play a key role in the hemodynamic deterioration of sustained VT and that the evaluation of baroreflex sensitivity in patients at high risk for sustained VT may become useful both in risk stratification and in the individualization of treatment.

Acetylcholinesterase-amyloid-beta-peptide interaction and Wnt signaling involvement in Abeta neurotoxicity.

Previous studies have indicated that acetylcholinesterase (AChE) promotes amyloid-beta-peptide (Abeta) fibril formation and AChE-Abeta complexes increase Abeta-dependent neurotoxicity. Here we present evidence for the: i) identification of the AChE motif that promotes amyloid formation, ii) in vivo effect of AChE on brain plaque formation, and iii) connection between AChE-Abeta neurotoxicity and the Wnt signal transduction pathway. Computer modeling, stereotaxic infusions and cell biological techniques were used to study the above problems. Results indicated that a 3.4 kDa AChE peptide promotes Abeta fibril formation. AChE infusion into rat hippocampus determines the appearance of anti-Abeta and thioflavine-S positive plaques, and AChE-Abeta toxicity on hippocampal cultures was blocked by lithium, an activator of the Wnt cascade. We suggest that AChE-Abeta/Abeta dependent neurotoxicity may result in loss of function of Wnt signaling components, and open the possibility that lithium may be considered as a candidate for therapeutic intervention in Alzheimer's disease pathology.

Amino acid metabolism and the liver in renal failure.

The study of amino acid metabolism across the splanchnic organs can be useful for investigating derangements in nitrogen metabolism in chronic renal insufficiency. For this purpose, arterial-hepatic venous differences for 19 free amino acids, ammonia and urea, determined in whole blood, were measured in six patients with chronic renal insufficiency and in six subjects with normal renal function. In normal conditions, the hepatosplanchnic bed significantly extracts glutamine, alanine, glycine, serine, threonine, lysine, arginine, phenylalanine, valine, tyrosine, histidine, leucine, and ammonia, and releases glutamate, citrulline, and urea. In chronic renal insufficiency, glutamine uptake decreases, serine, valine and ammonia uptake disappears, proline extraction becomes present, citrulline output is no longer detectable and glutamate release falls slightly. Furthermore, the splanchnic uptake of ammonia and the output of urea into the hepatic veins are markedly reduced. Since glutamine and ammonia are major substrates for urea synthesis, their lower uptakes, as observed in renal insufficiency, may be consistent with the reduced urea output. The changes in splanchnic metabolism observed in chronic renal insufficiency have a minor effect on the abnormalities in circulating amino acids. Finally, the splanchnic metabolism shows an important role in the homeostasis of circulating tyrosine and proline.

Effect of reflex vagal activation on frequency of ventricular premature complexes.

To evaluate the antiarrhythmic effect of reflex-induced vagal activation, phenylephrine was infused in 17 patients with frequent ventricular premature complexes (VPCs). The role of heart rate reduction in suppressing VPCs was explored by pacing the atria at the preinfusion levels. Baroreceptor activation was considered effective when a greater than or equal to 20% decrease in heart rate was observed. Ten patients (59%) achieved the target heart rate decrease (-29 +/- 5%), whereas in 7 (41%) the baroreceptor reflex was considered inadequate. In the former group ("responders"), heart rate decreased from 73 +/- 7 to 52 +/- 6 beats/min (p less than 0.0001). When heart rate was allowed to fluctuate, ectopic activity was completely abolished in 9 of 10 patients; mean number of VPCs decreased from 38 +/- 8 to 0.2 +/- 0.6/100 beats (p less than 0.0001). During pacing, VPCs reappeared but their mean number (22 +/- 10/100 beats) was still significantly reduced compared with control values (p = 0.003). In the "nonresponders," despite adequate blood pressure increases, VPC frequency was not affected. The QT interval lengthened during phenylephrine (392 +/- 17 ms) versus control conditions (372 +/- 18 ms, p = 0.0008) in the responders group, whereas no change was observed in the nonresponders. These results demonstrate that reflex vagal activation markedly reduces VPCs. This effect is only partially rate-dependent; direct and indirect electrophysiologic changes secondary to baroreflex activation are also likely to be involved.

Response of cytochrome a,a3 to carbon monoxide in canine hearts with prior infarcts.

The effects of moderate levels of carbon monoxide (CO) on the oxidation-reduction state of cytochrome a,a3 (cyt a,a3) were examined in the hearts of twelve dogs with a prior myocardial infarction. Exposure to ten minutes CO produced a carboxyhemoglobin (CO-Hb) level of 9.4%, a level experienced by heavy smokers. Accompanying the exposure to CO, cyt a,a3 became more reduced; 17.4% +/- 4.7%. Exposure to CO was accompanied by an increase of 33% +/- 4% in the rate of cyt a,a3 reduction following occlusion of the left circumflex coronary artery and a decrease of 24% +/- 8% in the rate of cyt a,a3 oxidation with release. There was also a decrease in the magnitude of cyt a,a3 reduction from 86% +/- 9% to 70% +/- 11%. These results indicate that moderate levels of CO trap cyt a,a3 in the reduced state which impairs the ability of the heart to recover from transient ischemic episodes.

Carbon monoxide and lethal arrhythmias.

The effect of acute exposure to carbon monoxide on ventricular arrhythmias was studied in a previously described chronically maintained animal model of sudden cardiac death. In 60 percent of dogs with a healed anterior myocardial infarction, the combination of mild exercise and acute myocardial ischemia induces ventricular fibrillation. The events in this model are highly reproducible, thus allowing study by internal control analysis. Dogs that develop ventricular fibrillation during the test of exercise and acute myocardial ischemia are considered at high risk for sudden death and are defined as "susceptible"; dogs that survive the test without a fatal arrhythmia are considered at low risk for sudden death and are defined as "resistant." In the current study, the effects of carboxyhemoglobin levels ranging from 5 to 15 percent were tested in resistant and susceptible dogs. A trend toward higher heart rates was observed at all levels of carboxyhemoglobin, although significant differences were observed only with 15 percent carboxyhemoglobin. This trend was observed at rest and during exercise in both resistant and susceptible dogs. In resistant animals, in which acute myocardial ischemia is typically associated with bradycardia even under the control condition, this reflex response occurred earlier and was augmented after exposure to carbon monoxide. This effect may depend on the increased hypoxic challenge caused by carbon monoxide, and thus on an augmentation of the neural reflex activation or a sensitization of the sinus node to acetylcholine induced by hypoxia. In both resistant and susceptible dogs, carbon monoxide exposure induced a worsening of ventricular arrhythmias in a minority of cases. This worsening was not reproducible in subsequent trials. These data indicate that acute exposure to carbon monoxide is seldom arrhythmogenic in dogs that have survived myocardial infarction. Nevertheless, the observation that carbon monoxide exposure increases heart rate at rest and during moderate exercise may have clinical implications relevant to patients with coronary artery disease.(ABSTRACT TRUNCATED AT 400 WORDS)

[Sudden death after myocardial infarction. Prediction based on the baroreceptor reflex]. / La mort subite après infarctus du myocarde. Prédiction par l'étude des réflexes barorécepteurs.

The authors report their experience of the evaluation of autonomic nervous system control by measuring the sensitivity of the baroreceptor reflex (SBR) in the animal and in humans after myocardial infarction. The SBR is expressed as the ratio between the variations in heart rate and systolic blood pressure recorded after an injection of phenylephrine. In the dog, with an experimental myocardial infarction and submitted to an exercise stress test + ischemia (by occlusion of a second coronary vessel), a fall in the SBR is predictive of ventricular fibrillation: the SBR was 9.1 +/- 6 ms/mmHg in "sensitive" animals who fibrillated, compared with 17.7 +/- 6.5 in "resistant" animals. In addition, if dogs with experimental infarction are submitted to daily physical training, the SBR increases from 5.4 +/- 1.2 to 16.3 +/- 5 ms/mmHg and VF does not occur during exercise stress testing + ischemia. Finally, the SBR before infarction is also predictive of the risk of VF during exercise stress test + ischemia and of mortality in the acute phase of myocardial infarction. In man, the SBR decreases after infarction and recovers at the third month. There is no correlation between the SBR and LV ejection fraction. In a study of 78 patients, 2-year mortality increased from 3 to 40% when the SBR was less than 3 ms/mmHg and from 10 to 50 p. 100 if only patients with LV ejection fractions of less than 50% were considered. The evaluation of autonomic neural reflexes by measuring the SBR is easy to perform at the bedside and provides informations about post-infarction prognosis independent of and complementary to the state of pump function.

[Guidelines for diagnosis and therapy of diabetic nephropathy]. / Linee Guida per la diagnosi e terapia della nefropatia diabetica.

The incidence of diabetes as cause of end-stage renal failure (ESRF) has significantly increased, and will continue to grow during the next few years. Moreover, diabetic nephropathy is associated with elevated cardiovascular morbidity and mortality. These guidelines focus on the possible intervention strategies to prevent and treat ESRF in diabetic patients. In normoalbuminuric patients, glycated haemoglobin levels less than and equal to 7.5% is mandatory for reducing the risk of incipient nephropathy. Furthermore, blood pressure levels < 130/80 mmHg are strongly recommended. In microalbuminuric patients, glycated hemoglobin levels below 7.5% and blood pressure levels below 130/80 mmHg (120/70-75 mmHg in patients < 50 years) are recommended. Moreover, there is evidence that inhibition of the rennin-angiotensin-aldosterone system, either by angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin II receptor antagonists (AIIRA) is able to reduce the incidence of overt nephropathy, regardless of blood pressure levels. Current guidelines recommed ACE-I as the first-choice drug in type 1 diabetes, while both ACE-I and AAIRA are considered first-choice therapy in type 2 diabetes. In proteinuric patients it is uncertain whether glycemic control affects the progression of nephropathy, which in turn is dramatically influenced by blood pressure. Optimal blood pressure levels are below 130/80 mmHg (120/70-75 mmHg in patients < 50 years). In type 1 diabetes there is consensus on the renoprotective role of ACE-1. In type 2 diabetes, two recent trials demonstrated that AIIRA are more effective than conventional therapy or calcium channel blockers in slowing down the progression of nephropathy. ACE-I are indeed recommended as first-choice drugs in type 1 diabetes while AIIRA are the first-choice agents for ESRF prevention in type 2 diabetes. Dialysis treatment should be started as soon as the creatinine clearance is reduced to about 10-15 mL/min. The choice of dialysis schedule should be individualized according to clinical and adequacy criteria (CAPD weekly Kt/V > or = 2 and single HD session Kt/V > or = 1.5). Simultaneous pancreas-kidney transplantation should be the first-choice therapeutic option in type 1 diabetes, while renal transplantation has been demonstrated to significantly improve the prognosis of type 2 diabetes patients with ESRF.

Hospital survival and long term quality of life after emergency institution of venoarterial ECMO for refractory circulatory collapse.

BACKGROUND: Thanks to significant technical improvements, VA-ECMO is increasingly used to reverse circulatory collapse refractory to standard treatments. METHODS: We studied patients who underwent VA-ECMO due to primary cardiogenic shock or cardiac arrest between January 2008 and June 2011 at our institution. Variables related to hospital survival were analyzed. Long-term survival and health-related quality of life were checked. RESULTS: VA-ECMO was instituted in 23 patients: 17 outpatients and 6 inpatients. Seven of the outpatients were admitted to hospital under ongoing CPR. In these pts, time to CPR was 7 min (6-8) and time to ECMO 93 min (74-107); after 20 hours (16-22), all these pts died. Among remaining 16 pts, 6 were bridged to heart transplant and 4 to heart recovery, 8 survived to hospital discharge and 7 were alive with high health-related quality of life after 46 months (36-54). Ongoing CPR, inotropic score and lactates at cannulation did not differ between survivors and non-survivors; duration of shock, SOFA score and serum creatinine at ECMO institution, and lactates and fluid balance after 36 hours were higher in non-survivors. Patients could be kept on spontaneous breathing for >30% of time while on VA-ECMO. CONCLUSION: Emergency VA-ECMO institution can reverse refractory acute cardiovascular collapse, provided it is carried out before significant organ dysfunction occurs. Light sedation and spontaneous breathing while on VA-ECMO can be well tolerated by patients, but related clinical benefits should be proved. Patients successfully bridged to heart recovery or transplant are candidates for long-term good quality of life.