Higher platelet cytochrome oxidase specific activity in surviving than in non-surviving septic patients

Introduction

In a previous study with 96 septic patients, we found that circulating platelets in 6-months surviving septic patients showed higher activity and quantity of cytochrome c oxidase (COX) normalized by citrate synthase (CS) activity at moment of severe sepsis diagnosis than non-surviving septic patients. The objective of this study was to estimate whether COX specific activity during the first week predicts 1-month sepsis survival in a larger cohort of patients.

Methods

Using a prospective, multicenter, observational study carried out in six Spanish intensive care units with 198 severe septic patients, we determined COX activity per proteins (COXact/Prot) in circulating platelets at day 1, 4 and 8 of the severe sepsis diagnosis. Endpoints were 1-month and 6-months mortality.

Results

Survivor patients (n = 130) showed higher COXact/Prot (P < 0.001) than non-survivors (n = 68) at day 1, 4 and 8 of severe sepsis diagnosis. More than a half of the 6-months survivor patients showed an increase in their COXact/Prot from day 1 to 8. However, most of the 1-month non-survivors exhibited a decrease in their COXact/Prot from day 1 to 8. Multiple logistic regression analyses showed that of platelet COXact/Prot > 0.30 mOD/min/mg at day 1 (P = 0.002), 4 (P = 0.006) and 8 (P = 0.02) was associated independently with 1-month mortality. Area under the curve of COXact/Prot at day 1, 4 and 8 to predict 30-day survival were 0.70 (95% CI = 0.63-0.76; P < 0.001), 0.71 (95% CI = 0.64-0.77; P < 0.001) and 0.71 (95% CI = 0.64-0.78; P < 0.001), respectively.

Conclusions

The new findings of our study, to our knowledge the largest series reporting data about mitochondrial function during follow-up in septic patients, were that septic patients that survive 1-month have a higher platelet cytochrome oxidase activity at moment of sepsis diagnosis and during the first week than non-survivors, and that platelet cytochrome oxidase activity at moment of sepsis diagnosis and during the first week could be used as biomarker to predict the clinical outcome in septic patients.     

New insights into the mechanisms involved in B-type natriuretic peptide elevation and its prognostic value in septic patients

Introduction

Elevated plasma B-type natriuretic peptide (BNP) levels in patients with critical sepsis (severe sepsis and septic shock) may indicate septic cardiomyopathy. However, multiple heterogeneous conditions may also be involved in increased BNP level. In addition, the prognostic value of BNP in sepsis remains debatable. In this study, we sought to discover potential independent determinants of BNP elevation in critical sepsis. The prognostic value of BNP was also evaluated.

Methods

In this observational study, we enrolled mechanically ventilated, critically septic patients requiring hemodynamic monitoring through a pulmonary artery catheter. All clinical, laboratory and survival data were prospectively collected. Plasma BNP concentrations were measured daily for five consecutive days. Septic cardiomyopathy was assessed on day 1 on the basis of left and right ventricular ejection fractions (EF) derived from echocardiography and thermodilution, respectively. Mortality was recorded at day 28.

Results

A total of 42 patients with severe sepsis (N = 12) and septic shock (N = 30) were ultimately enrolled. Daily BNP levels were significantly elevated in septic shock patients compared with those with severe sepsis (P ≤0.002). Critical illness severity (assessed by Acute Physiology and Chronic Health Evaluation II and maximum Sequential Organ Failure Assessment scores), and peak noradrenaline dose on day 1 were independent determinants of BNP elevation (P <0.05). Biventricular EFs were inversely correlated with longitudinal BNP measurements (P <0.05), but not independently. Pulmonary capillary wedge pressures (PCWP) and volume expansion showed no correlation with BNP. In septic shock, increased central venous pressure (CVP) and CVP/PCWP ratio were independently associated with early BNP values (P <0.05).Twenty-eight-day mortality was 47.6% (20 of 42 patients). Daily BNP values poorly predicted outcome; BNP on day 1 > 800 pg/ml (the best cutoff point) fairly predicted mortality, with a sensitivity%, specificity% and area under the curve values of 65, 64 and 0.70, respectively (95% confidence interval = 0.54 to 0.86; P = 0.03). Plasma BNP levels declined faster in survivors than in nonsurvivors in both critical sepsis and septic shock (P ≤0.002). In septic shock, a BNP/CVP ratio >126 pg/mmHg/ml on day 2 and inability to reduce BNP <500 pg/ml implied increased mortality (P ≤0.036).

Conclusions

The severity of critical illness, rather than septic cardiomyopathy, is probably the major determinant of BNP elevation in patients with critical sepsis. Daily BNP values are of limited prognostic value in predicting 28-day mortality; however, fast BNP decline over time and a decrease in BNP <500 pg/ml may imply a favorable outcome.     

The effect of microvascular obstruction and intramyocardial hemorrhage on contractile recovery in reperfused myocardial infarction: insights from cardiovascular magnetic resonance

Background

Following acute myocardial infarction (AMI), microvascular obstruction (MO) and intramyocardial hemorrhage (IMH) adversely affect left ventricular remodeling and prognosis independently of infarct size. Whether this is due to infarct zone remodeling, changes in remote myocardium or other factors is unknown. We investigated the role of MO and IMH in recovery of contractility in infarct and remote myocardium.

Methods

Thirty-nine patients underwent cardiovascular magnetic resonance (CMR) with T2-weighted and T2* imaging, late gadolinium enhancement (LGE) and myocardial tagging at 2, 7, 30 and 90 days following primary percutaneous coronary intervention for AMI. Circumferential strain in infarct and remote zones was stratified by presence of MO and IMH.

Results

Overall, infarct zone strain recovered with time (p < 0.001). In the presence of MO with IMH and without IMH, epicardial strain recovered (p = 0.03, p < 0.01 respectively), but mid-myocardial or endocardial strain did not (mid-myocardium: p = 0.05, p = 0.12; endocardium: p = 0.27, p = 0.05, respectively). By day 90, infarcts with MO had more attenuated strain in all myocardial layers compared to infarcts without MO (p < 0.01); those with IMH were attenuated further (p < 0.01). Remote myocardial strain was similar across groups at all time-points (p > 0.2). Infarct transmural extent did not correlate with strain (p > 0.05 at each time point). In multivariable logistic regression, MO and IMH were the only significant independent predictors of attenuated 90-day infarct zone strain (p = 0.004, p = 0.011, respectively).

Conclusions

Strain improves within the infarct zone overall following reperfusion with or without MO or IMH. Mid-myocardial and endocardial infarct contractility is diminished in the presence of MO, and further in the presence of IMH. MO and IMH are greater independent predictors of infarct zone contractile recovery than infarct volume or transmural extent.     

Quantitative assessment of magnetic resonance derived myocardial perfusion measurements using advanced techniques: microsphere validation in an explanted pig heart system

Background

Cardiovascular Magnetic Resonance (CMR) myocardial perfusion imaging has the potential to evolve into a method allowing full quantification of myocardial blood flow (MBF) in clinical routine. Multiple quantification pathways have been proposed. However at present it remains unclear which algorithm is the most accurate. An isolated perfused, magnetic resonance (MR) compatible pig heart model allows very accurate titration of MBF and in combination with high-resolution assessment of fluorescently-labeled microspheres represents a near optimal platform for validation. We sought to investigate which algorithm is most suited to quantify myocardial perfusion by CMR at 1.5 and 3 Tesla using state of the art CMR perfusion techniques and quantification algorithms.

Methods

First-pass perfusion CMR was performed in an MR compatible blood perfused pig heart model. We acquired perfusion images at physiological flow (“rest”), reduced flow (“ischaemia”) and during adenosine-induced hyperaemia (“hyperaemia”) as well as during coronary occlusion. Perfusion CMR was performed at 1.5 Tesla (n = 4 animals) and at 3 Tesla (n = 4 animals). Fluorescently-labeled microspheres and externally controlled coronary blood flow served as reference standards for comparison of different quantification strategies, namely Fermi function deconvolution (Fermi), autoregressive moving average modelling (ARMA), exponential basis deconvolution (Exponential) and B-spline basis deconvolution (B-spline).

Results

All CMR derived MBF estimates significantly correlated with microsphere results. The best correlation was achieved with Fermi function deconvolution both at 1.5 Tesla (r = 0.93, p < 0.001) and at 3 Tesla (r = 0.9, p < 0.001). Fermi correlated significantly better with the microspheres than all other methods at 3 Tesla (p < 0.002). B-spline performed worse than Fermi and Exponential at 1.5 Tesla and showed the weakest correlation to microspheres (r = 0.74, p < 0.001). All other comparisons were not significant. At 3 Tesla exponential deconvolution performed worst (r = 0.49, p < 0.001).

Conclusions

CMR derived quantitative blood flow estimates correlate with true myocardial blood flow in a controlled animal model. Amongst the different techniques, Fermi function deconvolution was the most accurate technique at both field strengths. Perfusion CMR based on Fermi function deconvolution may therefore emerge as a useful clinical tool providing accurate quantitative blood flow assessment.     

Variation in the use of renal replacement therapy in patients with septic shock: a substudy of the prospective multicenter observational FINNAKI study

Introduction

Indications for renal replacement therapy (RRT) have not been generally standardized and vary among intensive care units (ICUs). We aimed to assess the proportion, indications, and modality of RRT, as well as the association between the proportion of RRT use and 90-day mortality in patients with septic shock in Finnish adult ICUs.

Methods

We identified patients with septic shock from the prospective observational multicenter FINNAKI study conducted between 1 September 2011 and 1 February 2012. We divided the ICUs into high-RRT and low-RRT ICUs according to the median of the proportion of RRT-treated patients with septic shock. Differences in indications, and modality of RRT between ICU groups were assessed. Finally, we performed an adjusted logistic regression analysis to evaluate the possible association of the ICU group (high vs. low-RRT) with 90-day mortality.

Results

Of the 726 patients with septic shock, 131 (18.0%, 95% CI 15.2 to 20.9%) were treated with RRT. The proportion of RRT-treated patients varied from 3% up to 36% (median 19%) among ICUs. High-RRT ICUs included nine ICUs (354 patients) and low-RRT ICUs eight ICUs (372 patients). In the high-RRT ICUs patients with septic shock were older (P = 0.04), had more cardiovascular (P <0.001) and renal failures (P = 0.003) on the first day in the ICU, were more often mechanically ventilated, and received higher maximum doses of norepinephrine (0.25 μg/kg/min vs. 0.18 μg/kg/min, P <0.001) than in the low-RRT ICUs. No significant differences in indications for or modality of RRT existed between the ICU groups. The crude 90-day mortality rate for patients with septic shock was 36.2% (95% CI 31.1 to 41.3%) in the high-RRT ICUs compared to 33.9% (95% CI 29.0 to 38.8%) in the low-RRT ICUs, P = 0.5. In an adjusted logistic regression analysis the ICU group (high-RRT or low-RRT ICUs) was not associated with 90-day mortality.

Conclusions

Patients with septic shock in ICUs with a high proportion of RRT had more severe organ dysfunctions and received more organ-supportive treatments. Importantly, the ICU group (high-RRT or low-RRT group) was not associated with 90-day mortality.     

Close to recommended caloric and protein intake by enteral nutrition is associated with better clinical outcome of critically ill septic patients: secondary analysis of a large international nutrition database

Introduction

Current international sepsis guidelines recommend low-dose enteral nutrition (EN) for the first week. This contradicts other nutrition guidelines for heterogenous groups of ICU patients. Data on the optimal dose of EN in septic patients are lacking. Our aim was to evaluate the effect of energy and protein amount given by EN on clinical outcomes in a large cohort of critically ill septic patients.

Methods

We conducted a secondary analysis of pooled data collected prospectively from international nutrition studies. Eligible patients had a diagnosis of sepsis and/or pneumonia and were admitted to the ICU for ≥3 days, mechanically ventilated within 48 hours of ICU admission and only receiving EN. Patients receiving parenteral nutrition were excluded. Data were collected from ICU admission up to a maximum of 12 days. Regression models were used to examine the impact of calorie and protein intake on 60-day mortality and ventilator-free days.

Results

Of the 13,630 patients included in the dataset, 2,270 met the study inclusion criteria. Patients received a mean amount of 1,057 kcal/d (14.5 kcal/kg/day) and 49 g protein/day (0.7 g/kg/d) by EN alone. Patients were mechanically ventilated for a median of 8.4 days and 60-day mortality was 30.5%. An increase of 1,000 kcal was associated with reduced 60-day mortality (odds ratio (OR) 0.61; 95% confidence interval (CI) 0.48 to 0.77, P <0.001) and more ventilator-free days (2.81 days, 95% CI 0.53 to 5.08, P = 0.02) as was an increase of 30 g protein per day (OR 0.76; 95% CI 0.65 to 0.87, P <0.001 and 1.92 days, 95% CI 0.58 to 3.27, P = 0.005, respectively).

Conclusions

In critically ill septic patients, a calorie and protein delivery closer to recommended amounts by EN in the early phase of ICU stay was associated with a more favorable outcome.     

Aortic arch shape is not associated with hypertensive response to exercise in patients with repaired congenital heart diseases

Background

Aortic arch geometry is linked to abnormal blood pressure (BP) response to maximum exercise. This study aims to quantitatively assess whether aortic arch geometry plays a role in blood pressure (BP) response to exercise.

Methods

60 age- and BSA-matched subjects – 20 post-aortic coarctation (CoA) repair, 20 transposition of great arteries post arterial switch operation (ASO) and 20 healthy controls – had a three-dimensional (3D), whole heart magnetic resonance angiography (MRA) at 1.5 Tesla, 3D geometric reconstructions created from the MRA. All subjects underwent cardiopulmonary exercise test on the same day as MRA using an ergometer cycle with manual BP measurements. Geometric analysis and their correlation with BP at peak exercise were assessed.

Results

Arch curvature was similarly acute in both the post-CoA and ASO cases [0.05 ± 0.01 vs. 0.05 ± 0.01 (1/mm/m²); p = 1.0] and significantly different to that of normal healthy controls [0.05 ± 0.01 vs. 0.03 ± 0.01 (1/mm/m²), p < 0.001]. Indexed transverse arch cross sectional area were significantly abnormal in the post-CoA cases compared to the ASO cases (117.8 ± 47.7 vs. 221.3 ± 44.6; p < 0.001) and controls (117.8 ± 47.7 vs. 157.5 ± 27.2 mm²; p = 0.003). BP response to peak exercise did not correlate with arch curvature (r = 0.203, p = 0.120), but showed inverse correlation with indexed minimum cross sectional area of transverse arch and isthmus (r = -0.364, p = 0.004), and ratios of minimum arch area/ descending diameter (r = -0.491, p < 0.001).

Conclusion

Transverse arch and isthmus hypoplasia, rather than acute arch angulation plays a role in the pathophysiology of BP response to peak exercise following CoA repair.     

Calibration of myocardial T2 and T1 against iron concentration

Background

The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron.

Methods

Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n = 7) or cardiac transplantation (n = 4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1 = 1/T1 and R2 = 1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy.

Results

From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (±SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p < 0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R² 0.566, p < 0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R² 0.790, p < 0.001). The relation was [Fe] = 5081•(T2)^-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R² 0.517, p < 0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R² 0.657, p < 0.001).

Conclusion

Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies.     

Plasma adrenomedullin is associated with short-term mortality and vasopressor requirement in patients admitted with sepsis

Introduction

The incidence of death among patients admitted for severe sepsis or septic shock is high. Adrenomedullin (ADM) plays a central role in initiating the hyperdynamic response during the early stages of sepsis. Pilot studies indicate an association of plasma ADM with the severity of the disease. In the present study we utilized a novel sandwich immunoassay of bioactive plasma ADM in patients hospitalized with sepsis in order to assess the clinical utility.

Methods

We enrolled 101 consecutive patients admitted to the emergency department with suspected sepsis in this study. Sepsis was defined by fulfillment of at least two systemic inflammatory response syndrome (SIRS) criteria plus clinical suspicion of infection. Plasma samples for ADM measurement were obtained on admission and for the next four days. The 28-day mortality rate was recorded.

Results

ADM at admission was associated with severity of disease (correlation with Acute Physiology and Chronic Health Evaluation II (APACHE II) score: r = 0.46; P <0.0001). ADM was also associated with 28-day mortality (ADM median (IQR): survivors: 50 (31 to 77) pg/mL; non-survivors: 84 (48 to 232) pg/mL; P <0.001) and was independent from and additive to APACHE II (P = 0.02). Cox regression analysis revealed an additive value of serial measurement of ADM over baseline assessment for prediction of 28-day mortality (P < 0.01). ADM was negatively correlated with mean arterial pressure (r = -0.39; P <0.0001), and it strongly discriminated those patients requiring vasopressor therapy from the others (ADM median (IQR): no vasopressors 48 (32 to 75) pg/mL; with vasopressors 129 (83 to 264) pg/mL, P <0.0001).

Conclusions

In patients admitted with sepsis, severe sepsis or septic shock plasma ADM is strongly associated with severity of disease, vasopressor requirement and 28-day mortality.     

The development and implementation of a training package for dietitians on cow’s milk protein allergy in infants and children based on UK RCPCH competencies for food allergies – a pilot study

Background

Many food allergy guidelines have been published worldwide over recent years. The United Kingdom National Institute of Health and Clinical Excellence guidelines and The Royal College of Paediatrics and Child Health food allergy care pathways require dietitians to assist with the diagnosis and management of food allergies, which highlighted the need for further education of dietitians to meet these competencies. The aim of this study was to design a competence based one day education course for dietitians on the diagnosis and management of cow’s milk protein allergy in infants and children.

Methods

A one day training course was developed. Dietitians’ knowledge was assessed via multiple choice questions before and on the day of the course and retention of knowledge was assessed one month after the course. Pre course reading was given once the first assessment was completed.

Results

Thirty seven dietitians attended the course and 32 completed all three assessments. A significant improvement in assessment scores was seen between the pre course and on the day assessments of 7.2% (p < 0.001) and between pre course and post course assessments of 8.9% (p < 0.001). In delegates who rated their perceived level of knowledge as high, a significant increase was seen between pre course and on the day and between pre course and post course (both p < 0.001). Actual increase in knowledge was seen alongside a significant increase in high rating of perceived level of confidence between pre course and on the day and between pre course and post course (both p < 0.001).

Conclusions

Educating dietitians using the format of one day teaching with pre and post course assessment has improved both knowledge and competencies in the diagnosis and management of cow’s milk protein allergy. Further courses in other areas of food allergy could be developed using this approach within the UK and worldwide.     

Continuous venovenous hemofiltration versus extended daily hemofiltration in patients with septic acute kidney injury: a retrospective cohort study

Introduction

Whether continuous venovenous hemofiltration (CVVHF) is superior to extended daily hemofiltration (EDHF) for the treatment of septic AKI is unknown. We compared the effect of CVVHF (greater than 72 hours) with EDHF (8 to 12 hours daily) on renal recovery and mortality in patients with severe sepsis or septic shock and concurrent acute kidney injury (AKI).

Methods

A retrospective analysis of 145 septic AKI patients who underwent renal replacement therapy (RRT) between July 2009 and May 2013 was performed. These patients were treated by CVVHF or EDHF with the same polyacrylonitrile membrane and bicarbonate-based buffer. The primary outcomes measured were occurrence of renal recovery and all-cause mortality by 60 days.

Results

Sixty-five and eighty patients were treated with CVVHF and EDHF, respectively. Patients in the CVVHF group had significantly higher recovery of renal function (50.77% of CVVHF group versus 32.50% in the EDHF group, P = 0.026). Median time to renal recovery was 17.26 days for CVVHF patients and 25.46 days for EDHF patients (P = 0.039). Sixty-day all-cause mortality was similar between CVVHF and EDHF groups (44.62%, and 46.25%, respectively; P = 0.844). 55.38% of patients on CVVHF and 28.75% on EDHF developed hypophosphatemia (P = 0.001). The other adverse events related to RRT did not differ between groups. On multivariate analysis, including physiologically clinical relevant variables, CVVHF therapy was significantly associated with recovery of renal function (HR 3.74; 95% CI 1.82 to 7.68; P < 0.001), but not with mortality (HR 0.69; 95% CI 0.34 to 1.41; P = 0.312).

Conclusions

Patients undergoing CVVHF therapy had significantly improved renal recovery independent of clinically relevant variables. The patients with septic AKI had similar 60-day all-cause mortality rates, regardless of type of RRT.     

Coefficient of glucose variation is independently associated with mortality in critically ill patients receiving intravenous insulin

Introduction

Both patient- and context-specific factors may explain the conflicting evidence regarding glucose control in critically ill patients. Blood glucose variability appears to correlate with mortality, but this variability may be an indicator of disease severity, rather than an independent predictor of mortality. We assessed blood glucose coefficient of variation as an independent predictor of mortality in the critically ill.

Methods

We used eProtocol-Insulin, an electronic protocol for managing intravenous insulin with explicit rules, high clinician compliance, and reproducibility. We studied critically ill patients from eight hospitals, excluding patients with diabetic ketoacidosis and patients supported with eProtocol-insulin for < 24 hours or with < 10 glucose measurements. Our primary clinical outcome was 30-day all-cause mortality. We performed multivariable logistic regression, with covariates of age, gender, glucose coefficient of variation (standard deviation/mean), Charlson comorbidity score, acute physiology score, presence of diabetes, and occurrence of hypoglycemia < 60 mg/dL.

Results

We studied 6101 critically ill adults. Coefficient of variation was independently associated with 30-day mortality (odds ratio 1.23 for every 10% increase, P < 0.001), even after adjustment for hypoglycemia, age, disease severity, and comorbidities. The association was higher in non-diabetics (OR = 1.37, P < 0.001) than in diabetics (OR 1.15, P = 0.001).

Conclusions

Blood glucose variability is associated with mortality and is independent of hypoglycemia, disease severity, and comorbidities. Future studies should evaluate blood glucose variability.     

Headache prevalence and characteristics among adolescents in the general population: a comparison between retrospect questionnaire and prospective paper diary data

Background

In the present school-based study, a convenience sample of 237 adolescents in grade 6-9 and second year in high school (age 12-18 years) was recruited from a city and a smaller town. The aim of the study was to compare information on the prevalence and various characteristics of headaches not related to disease in a retrospect questionnaire and prospective daily recordings of headaches in a standard paper diary during a 3-week period.

Methods

Besides headache severity, number of headache days, intensity levels and duration of headache episodes were estimated with both assessment methods. Most of the school children suffered from tension-type headaches and a smaller portion of migraine attacks.

Results

The overall results showed that school children significantly (p < 0.001) overestimated headache intensity in questionnaires as compared to diary recordings, whereas they underestimated frequency (p < 0.001) and duration (p < 0.001) of headaches. While the correlations on headache severity, frequency and duration between retrospect information in questionnaires and prospective diary recordings were low, the agreement varied with levels of headache characteristics.

Conclusions

Our findings concur well with results from a few similar community studies on headache complaints in school-aged children. We recommend that prospective recordings in diaries should be systematically used in clinical practice but also in epidemiological surveys to increase the validity and reliability in estimates of point prevalence of headache complaints in children and adolescents.     

Relationship between coronary flow reserve evaluated by phase-contrast cine cardiovascular magnetic resonance and serum eicosapentaenoic acid

Background

Long-term intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs), especially eicosapentaenoic acid (EPA) is associated with a low risk for cardiovascular disease. Phase-contrast cine cardiovascular magnetic resonance (PC cine CMR) can assess coronary flow reserve (CFR). The present study investigates the relationship between CFR evaluated by PC cine CMR and the serum EPA.

Methods

We studied 127 patients (male, 116 (91%); mean age, 72.2 ± 7.4 years) with known or suspected coronary artery disease (CAD). X-ray coronary angiography revealed no significant coronary arterial stenoses (defined as luminal diameter reduction ≥50% on quantitative coronary angiogram (QCA) analysis) in all study participants. Breath-hold PC cine CMR images of the coronary sinus (CS) were acquired to assess blood flow of the CS both at rest and during adenosine triphosphate (ATP) infusion. We calculated CFR as CS blood flow during ATP infusion divided by that at rest. Patients were allocated to groups according to whether they had high (n = 64, EPA ≥ 75.8 μg/mL) or low (n = 63, EPA < 75.8 μg/mL) median serum EPA.

Results

CFR was significantly lower in the low, than in the high EPA group (2.54 ± 1.00 vs. 2.91 ± 0.98, p = 0.038). Serum EPA positively correlated with CFR (R = 0.35, p < 0.001). We defined preserved CFR as > 2.5, which is the previously reported lower limit of normal flow reserve without obstructive CAD. Multivariate analysis revealed that EPA is an independent predictor of CFR > 2.5 (odds ratio, 1.01; 95% confidence interval, 1.00 – 1.02, p = 0.008).

Conclusions

The serum EPA is significantly correlated with CFR in CAD patients without significant coronary artery stenosis.     

Gender specific patterns of age-related decline in aortic stiffness: a cardiovascular magnetic resonance study including normal ranges

Background

Young females exhibit lower cardiovascular event rates that young men, a pattern which is lost, or even reversed with advancing age. As aortic stiffness is a powerful risk factor for cardiovascular events, a gender difference with advancing age could provide a plausible explanation for this pattern.

Methods

777 subjects (♀n = 408, ♂n = 369) across a wide range of age (21–85 years) underwent cardiovascular magnetic resonance to assess aortic pulse wave velocity (PWV) and, in addition, aortic distensibility at three levels; 1) ascending aorta (Ao) and 2) proximal descending aorta (PDA) at the level of the pulmonary artery and 3) the abdominal aorta (DDA).

Results

There was a strong negative correlation between increasing age and regional aortic distensibility (Ao♀R-0.84, ♂R-0.80, PDA♀R-0.82, ♂R-0.77, DDA♀R-0.80, ♂R-0.71 all p < 0.001) and a strong positive correlation with PWV, (♀R0.53, ♂R 0.63 both p < 0.001). Even after adjustment for mean arterial pressure, body mass index, heart rate, smoking and diabetes, females exhibited a steeper decrease in all distensibility measures in response to increasing age (Ao♀-1.3 vs ♂-1.1 mmHg-1, PDA ♀-1.2 vs ♂-1.0 mmHg, DDA ♀-1.8 vs ♂-1.4 mmHg-1 per 10 years increase in age all p < 0.001). No gender difference in PWV increase with age was observed (p = 0.11).

Conclusion

Although advancing age is accompanied by increased aortic stiffness in both males and females, a significant sex difference in the rate of change exists, with females showing a steeper decline in aortic elasticity. As aortic stiffness is strongly related to cardiovascular events our observations may explain the increase in cardiovascular event rates that accompanies the menopausal age in women.     

Value of additional strain analysis with feature tracking in dobutamine stress cardiovascular magnetic resonance for detecting coronary artery disease

Background

Dobutamine stress cardiovascular magnetic resonance (DS-CMR) has been established for the detection of coronary artery disease (CAD). The novel technique feature tracking (FT) analyses left ventricular circumferential strain (Ecc) thus offering detailed information about myocardial deformation. The purpose of this study was to evaluate FT based Ecc for the detection of myocardial ischemia during DS-CMR.

Methods

A total of 25 patients (18 males; mean age 64 ± 10 years) with suspected or known CAD underwent a standardized high-dose DS-CMR protocol at 1.5 T. For FT analysis cine short axis (SAX) views (apical, medial, basal) at rest and during maximum dobutamine stress were used. None of the patients had wall motion abnormalities (WMAs) or impaired left ventricular function at rest or scar tissue. For analysis of Ecc the three SAX planes were divided into 16 segments (n = 400 segments). During stress 15 patients (34 segments) developed WMAs as assessed by visual analysis. All patients underwent x-ray coronary angiography for clinical reasons which served as the reference standard. Patients without WMAs during DS-CMR and exclusion of stenotic CAD were defined as normal (10 patients, 160 segments). In patients with significant CAD segments that were supplied by a vessel of >70% narrowing were defined as stenotic (n = 64). The remaining segments in patients with significant CAD were considered as remote (n = 176).

Results

At rest no differences in Ecc were observed between normal, stenotic and remote segments. High-dose dobutamine stress revealed highly significant differences between Ecc of normal and stenotic segments (p < 0.001), as well as between remote and stenotic segments (p < 0.001). The same observation took place for the absolute change of Ecc (p < 0.001 and p = 0.01). ROC analysis of Ecc during maximum DS-CMR differentiated normal from stenotic segments with a sensitivity of 75% and specificity of 67% using a cutoff -33.2% with an area under the curve of 0.78. Additional analysis of intermediate-dose dobutamine also showed a significant difference between normal and stenotic segments (p = 0.001).

Conclusion

FT based analysis of Ecc during intermediate- and high-dose DS-CMR was feasible and differentiated between stenotic, remote and normal segments. Quantitative assessment of Ecc with FT may improve the diagnostic accuracy of DS-CMR for detection of ischemia.     

Comparison of symptomatic and asymptomatic atherosclerotic carotid plaques using parallel imaging and 3?T black-blood in vivo CMR

Background

To determine if black-blood 3 T cardiovascular magnetic resonance (bb-CMR) can depict differences between symptomatic and asymptomatic carotid atherosclerotic plaques in acute ischemic stroke patients.

Methods

In this prospective monocentric observational study 34 patients (24 males; 70 ±9.3 years) with symptomatic carotid disease defined as ischemic brain lesions in one internal carotid artery territory on diffusion weighted images underwent a carotid bb-CMR at 3 T with fat-saturated pre- and post-contrast T1w-, PDw-, T2w- and TOF images using surface coils and Parallel Imaging techniques (PAT factor = 2) within 10 days after symptom onset. All patients underwent extensive clinical workup (lab, brain MR, duplex sonography, 24-hour ECG, transesophageal echocardiography) to exclude other causes of ischemic stroke. Prevalence of American Heart Association lesion type VI (AHA-LT6), status of the fibrous cap, presence of hemorrhage/thrombus and area measurements of calcification, necrotic core and hemorrhage were determined in both carotid arteries in consensus by two reviewers who were blinded to clinical information. McNemar and Wilcoxon''s signed rank tests were use for statistical comparison. A p-value <0.05 was considered statistically significant.

Results

Symptomatic plaques showed a higher prevalence of AHA-LT6 (67.7% vs. 11.8%; p < 0.001; odds ratio = 12.5), ruptured fibrous caps (44.1% vs. 2.9%; p < 0.001; odds ratio = 15.0), juxtaluminal thrombus (26.5 vs. 0%; p < 0.01; odds ratio = 7.3) and intraplaque hemorrhage (58.6% vs. 11.8%; p = 0.01; odds ratio = 3.8). Necrotic core and hemorrhage areas were greater in symptomatic plaques (14.1 mm² vs. 5.5 mm² and 13.6 mm² vs. 5.3 mm²; p < 0.01, respectively).

Conclusion

3 T bb-CMR is able to differentiate between symptomatic and asymptomatic carotid plaques, demonstrating the potential of bb-CMR to differentiate between stable and vulnerable lesions and ultimately to identify patients with low versus high risk for cardiovascular complications. Best predictors of the symptomatic side were a ruptured fibrous cap, AHA-LT 6, juxtaluminal hemorrhage/thrombus, and intraplaque hemorrhage.     

A novel risk score to predict 1-year functional outcome after intracerebral hemorrhage and comparison with existing scores

Introduction

Spontaneous intracerebral hemorrhage (ICH) is one of leading causes of mortality and morbidity worldwide. Several predictive models have been developed for ICH; however, none of them have been consistently used in routine clinical practice or clinical research. In the study, we aimed to develop and validate a risk score for predicting 1-year functional outcome after ICH (ICH Functional Outcome Score, ICH-FOS). Furthermore, we compared discrimination of the ICH-FOS and 8 existing ICH scores with regard to 30-day, 3-month, 6-month, and 1-year functional outcome and mortality after ICH.

Methods

The ICH-FOS was developed based on the China National Stroke Registry, in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Poor functional outcome was defined as modified Rankin Scale score (mRS) ≥3 at 1 year after ICH. Multivariable logistic regression was performed to determine independent predictors, and β-coefficients were used to generate scoring system of the ICH-FOS. The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration.

Results

The overall 1-year poor functional outcome (mRS ≥ 3) was 46.7% and 44.9% in the derivation (n = 1,953) and validation (n = 1,302) cohorts, respectively. A 16-point ICH-FOS was developed from the set of independent predictors of 1-year poor functional outcome after ICH including age (P < 0.001), admission National Institutes of Health Stroke Scale score (P < 0.001), Glasgow Coma Scale score (P < 0.001), blood glucose (P = 0.002), ICH location (P < 0.001), hematoma volume (P < 0.001), and intraventricular extension (P < 0.001). The ICH-FOS showed good discrimination (AUROC) in the derivation (0.836, 95% CI: 0.819-0.854) and validation (0.830, 95% CI: 0.808-0.852) cohorts. The ICH-FOS was well calibrated (Hosmer-Lemeshow test) in the derivation (P = 0.42) and validation (P = 0.39) cohort. When compared to 8 prior ICH scores, the ICH-FOS showed significantly better discrimination with regard to 1-year functional outcome and mortality after ICH (all P < 0.0001). Meanwhile, the ICH-FOS also demonstrated either comparable or significantly better discrimination for poor functional outcome and mortality at 30-day, 3-month, and 6-month after ICH.

Conclusion

The ICH-FOS is a valid clinical grading scale for 1-year functional outcome after ICH. Further validation of the ICH-FOS in different populations is needed.     

Treatment of heart failure in adults with thalassemia major: response in patients randomised to deferoxamine with or without deferiprone

Background

Established heart failure in thalassaemia major has a poor prognosis and optimal management remains unclear.

Methods

A 1 year prospective study comparing deferoxamine (DFO) monotherapy or when combined with deferiprone (DFP) for patients with left ventricular ejection fraction (LVEF) <56% was conducted by the Thalassemia Clinical Research Network (TCRN). All patients received DFO at 50–60 mg/kg 12–24 hr/day sc or iv 7 times weekly, combined with either DFP 75 at mg/kg/day (combination arm) or placebo (DFO monotherapy arm). The primary endpoint was the change in LVEF by CMR.

Results

Improvement in LVEF was significant in both study arms at 6 and 12 months (p = 0.04), normalizing ventricular function in 9/16 evaluable patients. With combination therapy, the LVEF increased from 49.9% to 55.2% (+5.3% p = 0.04; n = 10) at 6 months and to 58.3% at 12 months (+8.4% p = 0.04; n = 7). With DFO monotherapy, the LVEF increased from 52.8% to 55.7% (+2.9% p = 0.04; n = 6) at 6 months and to 56.9% at 12 months (+4.1% p = 0.04; n = 4). The LVEF trend did not reach statistical difference between study arms (p = 0.89). In 2 patients on DFO monotherapy during the study and in 1 patient on combined therapy during follow up, heart failure deteriorated fatally. The study was originally powered for 86 participants to determine a 5% difference in LVEF improvement between treatments. The study was prematurely terminated due to slow recruitment and with the achieved sample size of 20 patients there was 80% power to detect an 8.6% difference in EF, which was not demonstrated. Myocardial T2* improved in both arms (combination +1.9 ± 1.6 ms p = 0.04; and DFO monotherapy +1.9 ± 1.4 ms p = 0.04), but with no significant difference between treatments (p = 0.65). Liver iron (p = 0.03) and ferritin (p < 0.001) both decreased significantly in only the combination group.

Conclusions

Both treatments significantly improved LVEF and myocardial T2*. Although this is the largest and only randomized study in patients with LV decompensation, further prospective evaluation is needed to identify optimal chelation management in these high-risk patients.     

Quantitative assessment of paravalvular regurgitation following transcatheter aortic valve replacement

Background

Paravalvular aortic regurgitation (PAR) following transcatheter aortic valve implantation (TAVI) is well acknowledged. Despite improvements, echocardiographic measurement of PAR largely remains qualitative. Cardiovascular magnetic resonance (CMR) directly quantifies AR with accuracy and reproducibility. We compared CMR and transthoracic echocardiography (TTE) analysis of pre-operative and post-operative aortic regurgitation in patients undergoing both TAVI and surgical aortic valve replacement (AVR).

Methods

Eighty-seven patients with severe aortic stenosis undergoing TAVI (56 patients) or AVR were recruited. CMR (1.5 T) and transthoracic echocardiography (TTE) were carried out pre-operatively and a median of 6 days post-operatively. The CMR protocol included regurgitant aortic flows using through-plane phase-contrast velocity. None/trivial, mild, moderate and severe AR by CMR was defined as ≤8%, 9-20%, 21–39%, >40% regurgitant fractions respectively.

Results

Pre- and post-operative left ventricular ejection fraction (LVEF) was similar. Post-procedure aortic regurgitant fraction using CMR was higher in the TAVI group (TAVI 16 ± 13% vs. AVR 4 ± 4%, p < 0.01). Comparing CMR to TTE, 27 of 56 (48%) TAVI patients had PAR which was at least one grade more severe on CMR than TTE (Z = −4.56, p <0.001). Sensitivity analysis confirmed the difference in PAR grade between TTE and CMR in the TAVI group (Z = −4.49, p < 0.001).

Conclusion

When compared to CMR based quantitative analysis, TTE underestimated the degree of paravalvular aortic regurgitation. This underestimation may in part explain the findings of increased mortality associated with mild or greater AR by TTE in the PARTNER trial. Paravalvular aortic regurgitation post TAVI assessed as mild by TTE may in fact be more severe.