A novel risk score for severe ARDS patients undergoing ECMO after retrieval from peripheral hospitals.

BACKGROUND: Extracorporeal Membrane Oxygenation in severe ARDS unresponsive to conventional protective ventilation is associated with elevated costs, resource and complications, and appropriate risk stratification of candidate patients could be useful to recognize those more likely to benefit from ECMO. We aimed to derive a new outcome prediction score for patients retrieved by our ECMO team from peripheral centers, including systematic echocardiographic evaluation before ECMO start. METHODS: Sixty-nine consecutive patients with refractory ARDS requiring ECMO transferred from peripheral centers to our ICU (a tertiary ECMO referral center), from 1 October 2009 to 31 December 2015, were assessed. RESULTS: All patients were transported on ECMO (distance, median 77, range 4-456 km) The mortality rate was 41% (28/69). Our new risk score included age ≥ 42 years, BMI < 31 kg/m2 , RV dilatation, and pH < 7.35. The proposed cut off (Youden's index method) of nine had a sensitivity of 96% and a specificity of 30% (AUC-ROC: 0.85, 95% CI: 0.76-0.94, P < 0.001). When assessing the discriminatory ability of our risk score in the population of local patients, survivors had a mean value of 15.4 ± 8.6, whereas non-survivors showed a mean value of 20.1 ± 7.4 (P < 0.001). CONCLUSIONS: Our new risk score shows good discriminatory ability both in patients retrieved from peripheral centers and in those implanted at our center. This score includes variables easily available at bedside, and, for the first time, a pathophysiologic element, RV dilatation.

Pulmonary vascular dysfunction in refractory acute respiratory distress syndrome before veno-venous extracorporeal membrane oxygenation.

BACKGROUND: Pulmonary vascular dysfunction has been described in patients with acute respiratory distress syndrome (ARDS). Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a well-established treatment for these patients. We hypothesized that severe pulmonary vascular dysfunction and cor pulmonale identified by echocardiography before cannulation in these patients were associated with worse survival. METHODS: Echocardiography was used to identify pulmonary hypertension in 21 patients with refractory ARDS just before ECMO implantation. Survival was compared for those with and without cor pulmonale. RESULTS: In our series, the overall mortality rate was 57.1% (12/21). Echocardiographic exams were transthoracic in 5 patients (23.8%), transesophageal in 4 patients (19%), and both (transthoracic and transesophageal) in the remaining 12 patients (57.1%). In our series, six patients (28.5%) showed LV dysfunction. Acute cor pulmonale was detectable in 2 patients (9.5%), while the remaining 19 patients showed moderate pulmonary dysfunction. Survivors had a higher pre-cannulation LV ejection fraction (EF) (P = 0.02) and tricuspid annular plane excursion (P = 0.04), and lower peak systolic pulmonary artery pressures (P = 0.02). CONCLUSIONS: In patients with refractory ARDS immediately before ECMO implantation, the prevalence of acute cor pulmonale is low (9.5%). Survival is associated with higher LVEF and lower systolic pulmonary arterial pressure. These findings support the idea that echocardiographic assessment of pulmonary artery pressure in patients with refractory ARDS before VV-ECMO implantation may have value for risk-stratification.

The prognostic role of renal dysfunction in STEMI patients submitted to primary PCI with adjunctive thrombus aspiration.

AIM: The present investigation was aimed at assessing the prognostic impact of renal dysfunction rate in STEMI patients submitted to thrombectomy (TP). METHODS: Out of 1268 consecutive ST elevation myocardial infarction (STEMI) patients treated with pPCI from January 1rst 2004 to December 31th 2012 in our hospital 671 patients (52.9%) underwent adjunctive thrombus aspiration and constituted the study population. Patients were divided into three groups according to eGFR: group 1 included patients with eGFR>60 mL/min/m2, group 2 eGFR>30 mL/min/m2 and <60 mL/min/m2, group 3 eGFR<30 mL/min/m2. The rate of utilization of thrombectomy, the rate of pPCI failure and the incidence of major bleeding were assessed in each subgroup. Patients in group 3 and group 2 were less likely to be submitted to TP, while more than 50% of patients with normal eGFR underwent TP (overall P=0.019). The rate of pPCI failure was significantly higher in group 2 and 3 when compared to group 1 (P=0.002). Worsening renal failure was associated with a higher mortality rate both at ICCU and at 1 year follow-up (P<0.001 and P<0.001, respectively). A higher incidence of major bleedings was reported in group 2 and group 3, despite the lower administration of glycoprotein IIb/IIIa inhibitors (P<0.001). Moderate and severe renal impairment was associated with a higher mortality rate both at ICCU and at 1 year follow-up (P<0.001 and P<0.001, respectively). CONCLUSION: Thrombus aspiration is less like to be performed among patients with impaired renal function. Despite thrombus aspiration patients with reduced eGFR showed a higher incidence of pPCI failure.

The role of extracorporeal membrane oxygenation in donation after circulatory death.

Donor scarcity and the increased need for organ transplantation has prompted the development of an alternative source of donors to the more conventional brain dead donor. While in a Beating-Heart donor, abdominal and intrathoracic organs are perfused, in a non-beating heart donor (NHBD, or DCD), perfusion should be maintained, after confirmation of death, by means of ECMO and inflation of intra-aortic balloon accordingly to the localization of the organs that should be transplanted. In this setting, ECMO allows selective perfusion of the organs which should be transplanted ("compartmental ECMO"). The present review is aimed at summarizing the rationale for ECMO use in organ donation in DCD and the available evidence on this topic, as well as available evidence (in clinical studies) on normothermic organ preservation using ECMO in adults. Despite the fact that available studies suffer from methodological limitations (small cohorts, retrospective analysis, not always comparative), they all reach the same conclusion: the concept of extracorporeal support with oxygenation in DCD seems very promising since it has been reported to increase the available organ supply by approximately 20% to 25%2 by increasing the number of donors by approximately 33%. Centres with ECMO facilities should implement local programmes for donation after cardiac death (both in the emergency department and intensive care) using ECMO taking into account that this technique has been proven to increase donor pool.

Impact of age on the prognostic value of body mass index in ST-Elevation myocardial infarction.

BACKGROUND AND AIM: No data are so far available on the impact of age and obesity in ST-elevation myocardial infarction (STEMI) submitted to percutaneous coronary intervention (PCI). METHODS AND RESULTS: We assessed the impact of age on the prognostic value of body mass index (BMI) in 1268 consecutive STEMI patients admitted to our Intensive Cardiac Care Unit (ICCU). BMI categories were as follows: 37 "lean" patients (37/1268, 2.9%), 403 "normal" patients (403/1268, 31.8%), 656 "overweight" patients (656/1268, 51.7%), 172 "obese" patients (172/1268, 13.6%). Among patients aged <75 years, as BMI increased, the number of males and diabetic patients significantly increased (p < 0.001 and p = 0.004, respectively). Among STEMI patients aged ≥75 years, lean patients showed a higher in-ICCU mortality in respect to the other BMI categories but this did not reach statistical significance. BMI was an independent predictor of In-ICCU mortality in the whole population (lean vs. "normal": OR 3.47, 95%CI 1.08-11.14, p = 0.036) and it was associated with long term mortality only in patients <75 years since lean and overweight patients showed lower survival rate (lean vs. "normal": HR 9.25, 95%CI 3.09-27.63, p < 0.001; overweight vs. "normal": OR 2.10; 95%CI 1.04-4.23, p = 0.039). CONCLUSIONS: In our series, underweight is associated with the highest mortality across all age subgroups, while only in patients <75 years, overweight patients showed increased in-hospital mortality rate and a poorer long term survival rate. According to our data, the "so called obesity paradox" should be probably age-contextualized.

MicroRNA profiling reveals that miR-21, miR486 and miR-214 are upregulated and involved in cell survival in Sézary syndrome.

Sézary syndrome (SS) is an incurable leukemic variant of cutaneous T-cell lymphoma and its pathogenesis is still unknown. Diagnosis/prognosis may strongly ameliorate the management of SS individuals. Here, we profiled the expression of 470 microRNAs (miRNAs) in a cohort of 22 SS patients, and we identified 45 miRNAs differentially expressed between SS and controls. Using predictive analysis, a list of 19 miRNAs, including miR-21, miR-214, miR-486, miR-18a, miR-342, miR-31 and let-7 members were also found. Moreover, we defined a signature of 14 miRNAs including again miR-21, potentially able to discriminate patients with unfavorable and favorable outcome. We validated our data for miR-21, miR-214 and miR-486 by qRT-PCR, including an additional set of array-independent SS cases. In addition, we also provide an in vitro evidence for a contribution of miR-214, miR-486 and miR-21 to apoptotic resistance of CTCL cell line.

Glucose metabolism in cardiovascular surgery.

During the past few years, it has become evident that metabolic control is a major determinant of postoperative outcomes, not only for diabetic patients but for all patients undergoing surgery.In cardiac and vascular surgery, myocardial ischemia is a common challenge and the management of hyperglycemia should be part of the strategy aimed at optimizing cardiac protection during these types of surgery, since performed in high risk patients. Little informations are available on the relation between glucose substrate and the type of anesthesia and few studies have been performed on glucose metabolism in the perioperative risk assessment as well as on intraoperative and post surgical management of hyperglycemia in patients submitted to cardiac and vascular surgery. Evidence exists that even slight increased in glycemia are detrimental for patients (diabetic and non) elective for cardiac and vascular surgery, though the precise details of the timing of insulin therapy, the desired target serum glucose level, and the duration of therapy are so far to be completely elucidated. Anesthestiologists can therefore affect outcome by simply preserving a normal blood glucose concentration initiating in the operating room. The challenge to optimize glucose control should begin during preoperative evaluation.

Kinetic of procalcitonin in patients with cardiogenic shock following acute myocardial infarction: preliminary data.

INTRODUCTION: Procalcitonin concentrations are considered as a component of the inflammatory response and as an acute-phase marker, after shock or tissue injury (i.e. burn, trauma, surgery) or infections and sepsis. No data are so far available on the dynamics of procalcitonin levels in patients with cardiogenic shock following ST-elevation myocardial infarction, with no clinical or laboratory sign of infection. METHODS: We evaluated procalcitonin values every day during intensive cardiac care staying in ten cardiogenic shock patients admitted to our intensive cardiac care unit. NT-pro Brain Natriuretic Peptide, C Reactive Protein and APACHE II score were also assessed. RESULTS: Six patients survived, whereas 4 patients died. A progressive reduction in procalcitonin values was observed in cardiogenic shock patients who survived, whereas the lack of changes in procalcitonin concentrations was documented in cardiogenic shock patients who died (survivors: slope = -3.76; dead: slope = -0.81, p=0.004). Furthermore, higher values of glycemia, NT-pro Brain Natriuretic Peptide and C Reactive Protein (as well as higher APACHE II scores) were detectable in dead patients in respect to survivors. CONCLUSIONS: In our preliminary study we observed that in patients with cardiogenic shock and no sign of infections a reduction of procalcitonin levels was detectable only in survivors. Moreover, higher values of NT- Brain Natriuretic Peptide, a marked systemic inflammation (higher values of C Reactive Protein) and higher severity score (as depicted by APACHE II) are associated with an ominous prognosis in cardiogenic shock patients.

The Tcl1 oncogene defines secondary hair germ cells differentiation at catagen-telogen transition and affects stem-cell marker CD34 expression.

Overexpression of the TCL1 gene family plays a role in the onset of T-cell leukemias in mice and in humans. The Tcl1 gene is tightly regulated during early embryogenesis in which it participates in embryonic stem (ES)-cells proliferation and during lymphoid differentiation. Here, we provide evidences that Tcl1 is also important in mouse hair follicle (HF) and skin homeostasis. We found that Tcl1(-/-) adult mice exhibit hair loss, leading to alopecia with extensive skin lesions. By analysing Tcl1 expression in the wild-type (wt) skin through different stages of hair differentiation, we observe high levels in the secondary hair germ (HG) cells and hair bulges, during early anagen and catagen-telogen transition phases. The loss of Tcl1 does not result in apparent skin morphological defects during embryonic development and at birth, but its absence causes a reduction of proliferation in anagen HFs. Importantly, we show the that absence of Tcl1 induces a significant loss of the stem-cell marker CD34 (but not alpha6-integrin) expression in the bulge cells, which is necessary to maintain stem-cell characteristics. Therefore, our findings indicate that Tcl1 gene(s) might have important roles in hair formation, by its involvement in cycling and self-renewal of transient amplifying (TA) and stem-cell (SC) populations.

Hemodynamic goal-directed therapy. A review.

Patients can show arterial pressure and cardiac index within the normal range and still be in circulatory shock if oxygen and metabolic demand is increased or blood flow distribution is altered.Lactate is produced in anaerobic environment to preserve cellular integrity and physicians use its blood concentration value as a reliable marker of tissue hypoxia and energy failure.The authors review the recent literature on the importance of mixed venous oxygen saturation (SvO(2)) as an early sign of inadequate DO(2) that precede the lactate production.

Most Care®: a minimally invasive system for hemodynamic monitoring powered by the Pressure Recording Analytical Method (PRAM).

Invasive hemodynamic monitoring is a cornerstone of the care of critically ill and hemodynamically unstable patients in both intensive care units and operating rooms. The assessment of cardiac output by means of the pulmonary artery catheter has been considered the clinical gold standard. Nevertheless, several concerns have been raised regarding its invasiveness, usefulness, and associated complica-tions. These disadvantages have led to the development, during the last years, of a number of less invasive technologies for cardiac output determination. Among them, those based on the analysis of a peripheral arterial waveform have become commonly used. Most Care(®) is a minimally invasive arterial pressure based monitor powered by the Pressure Recording Analytical Method (PRAM), the only algorithm that does not require prior calibration or pre-calculated parameters and which is based of flow. PRAM provides the measurement of the main factors of hemodynamics, such as systemic blood pressures, stroke volume, cardiac output, and vascular resistances. Moreover, dynamic indices of fluid responsiveness are continuously displayed. In the present paper, we reviewed the current literature focusing on advantages and limitations of PRAM.

Adiponectin and the cardiovascular system: from risk to disease.

Adiponectin is known to play a role in fatty acid and glucose metabolism through a change in insulin sensitivity and activation of fuel oxidation by AMP-activated protein kinase. Adiponectin can be considered an important factor able to modulate the adipovascular axis which, through genomic and environmental influences, affects the cardiovascular risk milieu, from the pre-metabolic syndrome-- through the metabolic syndrome--to the overt atherosclerotic process and its clinical manifestations. Hypoadiponectinaemia can be viewed as an early sign of a complex cardiovascular risk factor predisposing to the atherosclerosis process as well as a contributing factor accelerating the progress of the atherosclerotic plaque. In addition, adiponectin per se holds a protective role thanks to its anti-inflammatory and antiatherogenic properties. The early identification of patients "at cardiovascular risk" means in the current practice to search for indexes of metabolic derangements and pro-inflammatory status (adiponectin) from adolescence and childhood.

Cardiac autonomic tone during trandolapril-irbesartan low-dose combined therapy in hypertension: a pilot project.

Pharmacological and clinical studies on the effects of angiotensin-converting enzyme (ACE) inhibitors support the idea of a central role played Angiotensin II which is able to cause cardiovascular and renal diseases also independently of its blood pressure elevating effects. The present investigation was aimed at evaluating the effect(s) of three different pharmacological regimens on both blood pressure and sympathetic drive in uncomplicated essential hypertension, by means of blood pressure laboratory measurements and ambulatory monitoring, 24-h heart rate variability and plasma noradrenaline levels. Thus, an ACE-inhibitor monotherapy (trandolapril, 2 mg/day), an AT(1)-receptor antagonist monotherapy (irbesartan, 300 mg/day), their low-dose combination (0.5 mg/day plus 150 mg/day, respectively) and placebo were given, in a randomised, single-blind, crossover fashion for a period of 3 weeks each to 12 mild essential hypertensives. Power spectral analysis (short recordings) and noradrenaline measurements were also performed in the supine position and after a postural challenge (60 degrees head-up tilting test: HUT). The low-dose combination therapy induced the greatest reduction in LF component and in LF/HF ratio, both in the resting and tilted positions, as well as in blood pressure. However, the physiological autonomic response to HUT was maintained. Noradrenaline plasma levels were lower after the combined therapy than after each drug alone. Our data demonstrate that in mild and uncomplicated essential hypertension, the chronic low-dose combination therapy with an ACE-inhibitor and an AT(1)-antagonist is more effective than the recommended full-dose monotherapy with either drug in influencing the autonomic regulation of the heart, suggesting a relative reduction in sympathetic drive both at cardiac and systemic levels.

Centrally mediated effects of bromocriptine on cardiac sympathovagal balance.

Bromocriptine, a dopamine agonist, is known to lower cardiovascular mortality in L-dopa-treated patients with Parkinson's disease, probably by reducing the cardiac sympathetic activity. We aimed at unmasking the central effects of bromocriptine on the heart by power spectrum analysis. Ten healthy subjects (aged 31+/-2 years) in supine and sitting positions were evaluated after the administration of bromocriptine (2.5 mg) alone and after pharmacological peripheral D(2)-like blockade by domperidone (20 mg). We calculated (autoregressive method) the following: the low-frequency (LF) component (an index of cardiac sympathetic tone), the high-frequency (HF) component (an index of cardiac vagal tone), and the LF/HF ratio (an index of cardiac sympathovagal balance). With subjects in the supine position, bromocriptine alone induced a significant increase in the LF component and the LF/HF ratio, together with a reduction in norepinephrine plasma levels and blood pressure values. These conflicting effects can be explained as the combined result of direct and indirect (reflex-mediated) actions of bromocriptine in vivo. No changes in cardiac autonomic drive were observed with subjects in the sitting position. After domperidone pretreatment, bromocriptine induced a reduction in the LF component and in the LF/HF ratio. The sitting position caused an increase in heart rate and in the LF/HF ratio. We demonstrated both peripheral and central effects of bromocriptine. In particular, pretreatment with a peripheral antagonist (domperidone) allowed us to unmask the central effect of bromocriptine on cardiac sympathetic drive.

Altered values of heart rate variability in patients with relapse of atrial fibrillation during the first week after electrical cardioversion: preliminary data.

BACKGROUND: It has not so far been elucidated whether the autonomic nervous system plays a role in the pathogenesis of atrial fibrillation relapse after electrical cardioversion. METHODS: In 40 consecutive patients with atrial fibrillation (22 males, 18 females, mean age 60 +/- 2 years) submitted to successful electrical cardioversion (external in 26 and low-energy internal in 14) we evaluated the heart rate variability (24-hour Holter recording) immediately after restoration of sinus rhythm in order to assess the cardiac sympatho-vagal drive. RESULTS: Patients with atrial fibrillation relapse within the first week of electrical cardioversion were characterized by a significantly higher low/high frequency ratio. CONCLUSIONS: Despite the heterogeneity of the studied population (concerning both the therapy and etiology of atrial fibrillation), our data strongly suggest that the evaluation of the low/high frequency ratio by means of power spectral analysis immediately after electrical cardioversion is a useful tool for the identification of those patients who are prone to atrial fibrillation recurrence. Our conclusions are supported by the finding of high positive and negative predictive values for the low/high frequency ratio both in the 24-hour period and during daytime.

Cardiovascular function in pregnancy: effects of posture.

OBJECTIVE: To evaluate the cardiovascular response to active postural changes in pregnancy. DESIGN: Prospective study. SETTING: Outpatient Clinic, Fetal Maternity Unit. PARTICIPANTS: Sixteen healthy women referred prior to pregnancy. METHODS: Heart rate, arterial pressure, echocardiographic end-diastolic and end-systolic left ventricular volumes (Teichholz' s formula) were measured in the three months before pregnancy, at the end of the first and second trimester, at mid third trimester, and six months after delivery in the supine and standing position, in thirteen women (mean age 33, range 25-38 years). RESULTS: Cardiac output (supine position) significantly increased (28%): it reached its maximum at the second trimester, remained steadily elevated in the mid third trimester, and returned to baseline after delivery. Cardiac output increased during pregnancy also in the active orthostatic position, the percentage increase being greater (70%) since the standing pre-conception value was lower. The postural stress induced similar changes in heart rate, arterial pressure and left ventricular ejection fraction before, during and after pregnancy. However, the reduction in cardiac output associated with early standing attenuated significantly at the second trimester and it was absent at mid third trimester (F = 3.13, P = 0.021). This was due to the interplay between the significantly lesser increase in systemic vascular resistance, occurring since the first trimester, and the significantly lesser decrease in left ventricular end-diastolic volume which was observed in the mid third trimester. CONCLUSION: These data indicate that the elevated cardiac output is adequately maintained in pregnancy during the postural challenge, due to optimisation of the responses of preload and afterload.

[Arrhythmia risk stratification based on clinical and functional data]. / Stratificazione del rischio aritmico alla luce dei dati clinici e funzionali.

The term "sudden death" indicates a natural and rapid death, an unexpected event in patients with high mortality rates such as those with heart failure. Sudden death in patients with heart failure is responsible for some of 40% of all deaths. A detailed clinical evaluation in patients with heart failure is extremely helpful for risk stratification. Although sex has been shown to have no prognostic relevance, heart failure due to coronary artery disease is associated with a higher mortality rate when compared to other etiologies. Left ventricular ejection fraction is the independent risk factor with the highest predictive value of survival. However, in patients with heart failure, except for the advanced stages, sudden death shows an incidence comparable with that of progressive pump failure. Like left ventricular ejection fraction, even the functional classifications of heart failure (such as NYHA) are to be considered as a non-specific marker of overall mortality. In fact, despite the close relation between advanced disease stages and a higher mortality rate, a large overlap has been demonstrated for the intermediate classes. The noninvasive assessment of oxygen consumption during cardiopulmonary exercise testing has been recognized as an independent risk factor and patients with a peak oxygen consumption < 10 ml/kg/min should be recommended for cardiac transplantation. In these patients no clear relation with an increased risk of sudden death has been demonstrated. In conclusion, the commonly employed clinical-functional indexes (left ventricular ejection fraction, functional classifications, peak oxygen consumption during cardiopulmonary testing) are significant predictors of overall mortality, however they are useless in the risk stratification for death due to fatal arrhythmias.

Effects of low-dose adrenomedullin on cardiac function and systemic haemodynamics in man.

The cardiovascular effects of low-dose adrenomedullin (ADM, 1, 2 and 3 pmol kg-1 min-1 for 30 min each) were evaluated in six healthy subjects in a placebo controlled, cross-over study by determining cardiac volumes, systolic and diastolic function (echocardiography) and systemic haemodynamics before, during and after ADM or placebo. High-resolution ultrasound was used to evaluate changes in carotid artery distension. ADM caused a +85% increment in its plasma levels and significantly increased plasma cyclic adenyl monophosphate (cAMP). Compared with placebo, ADM induced significant decrements in left ventricular (LV) systolic diameter and systemic vascular resistance, and increments in LV posterior wall thickening, ejection fraction and cardiac index. Right and left atrial emptying fraction and carotid artery distention increased. LV diastolic function, heart rate, and plasma renin activity did not change, whereas packed cell volume increased. These results indicate that ADM influences cardiovascular function and systemic haemodynamics at physiological plasma levels in man mainly because of its vasodilating activity, leading to reduced afterload.