Coronary Embolism Among Patients With ST-Segment-Elevation Myocardial Infarction and Atrial Fibrillation: An Underrecognized But Deadly Association.

BACKGROUND: The prevalence and impact of coronary emboli (CE) in patients with ST-segment-elevation myocardial infarction (STEMI) and atrial fibrillation (AF) have not been specifically studied. The objective was to describe the clinical characteristics and outcomes of patients with AF and CE in a large series of patients with STEMI. METHODS AND RESULTS: We investigated 2292 consecutive patients with STEMI and among them 225 patients with AF: 46 patients with a STEMI related to CE (group A) and 179 patients with a STEMI related to an atherosclerotic cause (group B). Compared with the 2067 patients without AF and CE (group C), patients with AF and CE were older (73 versus 59 years, P<0.05), more likely to be female (43% versus 22%, P<0.05), and presented more frequently with cardiogenic shock at admission (26% versus 9%, P<0.05). The baseline characteristics of patients with AF (group A versus B) did not differ significantly according to STEMI pathogenesis. In the unadjusted analysis, the 45-day mortality was higher in patients with CE and AF (group A versus group C: 20% versus 4%; P<0.05 and group A versus group B: 20% versus 8%, P=not significant); this trend persisted at 2-year follow-up (group A versus group C: 24% versus 6%; P<0.05 and group A versus group B: 24% versus 17%, P=not significant). After stabilized inverse exposure probability weighting adjustment, a higher 45-day mortality rate was confirmed in patients with CE and AF (group A versus group C: 18% versus 5%, P<0.05). CONCLUSIONS: In patients presenting with STEMI and AF, CE was associated with excess early mortality. REGISTRATION: URL: clinicaltrials.gov. Identifier: NCT05679843.

Impact of Simulation-Based Training on Radiation Exposure of Young Interventional Cardiologists.

Reducing radiation exposure during cardiovascular catheterization is of paramount importance to ensure patient and staff safety. Our study aimed to assess the transferability of acquired skills from virtual reality to the real world, including radioprotection measures during mentored simulation training (ST) in coronary angiography. A total of 10 cardiology residents were evaluated during real-life cases in the catheterization laboratory before (group A) and after mentored ST. The educational effect of mentored simulator training on real-life case performance was evaluated at 2 different time points: within the first week (group B) and after 12 weeks (group C). Compared with group A, the total dose area product (DAP) (µGy•m2) and total air kerma (mGy) were lower after ST: group A: 2,633 (1,723 to 3,617) versus group B: 1,618 (1,032 to 2,562), p <0.05 and 214 (136 to 297) versus 135 (84 to 222), p <0.05, respectively. Concerning operator radiation exposure (µSv), left finger dose: 1,090 (820 to 1,460) versus 635 (300 to 900), p = 0.028; left leg dose 80 (0 to 110) versus 0 (0 to 0), p = 0.027; left eye lens dose: 39 (24 to 69) versus 11 (8 to 20), p <0.0001; and chest dose outside the lead apron: 50 (34 to 88) versus 29 (21 to 50), p <0.003 were significantly lower in the group B than group A. A total of 12 weeks after ST, the total DAP and total air kerma remained stable along with operator exposure except left eye lens dose (µSv): group B: 11 (8 to 20) versus group C: 16 (12 to 27), p = 0.02. In addition, left eye lens dose, left wrist dose, and chest dose outside the lead apron were significantly correlated with total DAP (rs = 0.635, rs = 0.729, and rs = 0, 629, respectively) and total air kerma (rs = 0.488, rs = 0.514, and rs = 0.548, respectively) at 12 weeks. In conclusion, ST for coronary angiography may improve radioprotection learning and should be incorporated into training curricula.

Outcomes of patients with decreased arterial oxyhaemoglobin saturation on pulmonary arterial hypertension drugs.

BACKGROUND: Drugs approved for the treatment of pulmonary arterial hypertension (PAH) improve long-term outcomes. These drugs have pulmonary vasodilator properties which may potentially cause a decrease in arterial oxyhaemoglobin saturation (S aO2 ) in some patients. The present retrospective study of the French Pulmonary Hypertension Registry aimed to describe the clinical characteristics and outcomes of patients showing a ≥3% decrease in S aO2 while treated with PAH drugs. METHODS: We reviewed 719 PAH patients. The exclusion criteria were PAH associated with congenital heart disease and PAH with overt features of venous/capillaries involvement. RESULTS: 173 (24%) patients had a ≥3% decrease in S aO2 . At diagnosis, they were older with a lower diffusing capacity of the lung for carbon monoxide and a shorter 6-min walk distance compared with those who did not display a ≥3% decrease in S aO2 . The percentage of patients meeting the European Society of Cardiology/European Respiratory Society (ESC/ERS) low-risk criteria at re-evaluation was significantly lower in those with a ≥3% decrease in S aO2 and more patients started long-term oxygen therapy in this group (16% versus 5%; p<0.001). A ≥3% decrease in S aO2 was associated with a poorer survival (hazard ratio 1.81, 95% CI 1.43-2.34; p<0.0001). In a multivariate Cox analysis, a ≥3% decrease in S aO2 was a prognostic factor independent of age at diagnosis and ESC/ERS risk stratification at follow-up. CONCLUSIONS: When treated with PAH drugs, a large subset of patients experience a ≥3% decrease in S aO2 , which is associated with worse long-term outcomes and reduced survival.

Reduced Diuretic Dose in Patients Treated With Eplerenone: Data From the EPHESUS Trial.

BACKGROUND: Loop diuretics are used for congestion relief, and dose adaptations are usually a consequence of the clinicians' clinical judgement about the congestive status of the patient. In EPHESUS (Eplerenone in Patients With Systolic Dysfunction After Myocardial Infarction), many patients required diuretics for congestion relief. We thus hypothesized that blinded allocation to eplerenone would lead clinicians to reduce loop diuretics, as a consequence of the improvement in patients' status. METHODS: Cox and mixed-effects models were used over a median follow-up of 1.3 years in 6632 patients. RESULTS: A total of 6632 patients were included; at baseline, 3352 (50.5%) did not have diuretics, 2195 (33.1%) had diuretic doses between 1 and 40 mg/day, and 1085 (16.4%) had diuretic doses >40 mg/day. Patients with higher furosemide equivalent doses had a worse clinical status. Both baseline and follow-up incremental loop diuretic doses were associated with worse prognosis. Eplerenone treatment was associated with lower prescribed loop diuretic doses throughout the follow-up; lower doses were observed at 90 days and decreased further at 180 days and beyond. Eplerenone treatment led to a mean furosemide equivalent dose reduction of -2.2 mg/day (-2.9 to -1.6) throughout the follow-up. Eplerenone was effective in reducing morbidity and mortality regardless of the baseline loop diuretic dose used: hazard ratio for the outcome of cardiovascular death or heart failure hospitalization was 0.83 ([95% CI, 0.75-0.92]; P for interaction, 0.54). CONCLUSIONS: Eplerenone treatment led to a loop diuretic dose reduction during follow-up without evidence of treatment effect modification by loop diuretics. These findings suggest that eplerenone reduces congestive signs and symptoms, which enables clinicians to reduce loop diuretic doses.

Correlation of laboratory haemoconcentration measures with filling pressures obtained via pulmonary arterial pressure sensors in ambulatory heart failure patients.

AIMS: Laboratory measures of haemoconcentration correlate with invasive haemodynamics and clinical outcomes in hospitalized heart failure (HF) patients. We aimed to determine the association between haemoconcentration and haemodynamic measures in ambulatory HF patients with implantable pulmonary arterial pressure (PAP) sensors. METHODS AND RESULTS: We reviewed ambulatory HF patients (n = 23) managed at the Brigham and Women's Hospital with implantable PAP sensors (CardioMEMS™, Abbott, Atlanta, GA, USA) who had sufficient data for serial haemodynamic-haemoconcentration correlation. The primary measures of interest were the absolute changes in haemoglobin and diastolic PAP at follow-up compared to baseline values (obtained at implantation). In 23 patients (median age 64 years, 57% with HF with preserved ejection fraction), 518 paired laboratory-haemodynamic measurements were evaluated. At a median follow-up of 27 (interquartile range 13-42) months, 17 (74%) patients had at least one hospitalization (59 total hospitalizations including 30 HF hospitalizations). For the population as a whole, diastolic PAP was negatively correlated with haemoglobin level (r = -0.09, P = 0.053). This negative correlation was more apparent when changes in haemoglobin and diastolic PAP were evaluated at the time of HF hospitalization compared to baseline values (r = -0.40, P = 0.029). The mean rise in diastolic PAP of 3.6 mmHg at HF hospitalization corresponded to a numerical decline of 0.6 g/dL in haemoglobin (P = 0.20). CONCLUSION: Change in haemoglobin was correlated with change in diastolic PAP in ambulatory HF patients, especially at the time of HF hospitalization. These findings support the potential for investigation into the role of ambulatory monitoring of haemoglobin as an inexpensive, non-invasive tool to guide de-congestion strategies and potentially prevent HF hospitalizations.

Daily home monitoring of potassium, creatinine, and estimated plasma volume in heart failure post-discharge.

AIMS: Congestive status, serum potassium, and renal function are major determinants of outcomes as well as critical elements for adjusting drug therapy in heart failure (HF) patients. This study aimed at describing the daily variations in estimated plasma volume (ePV, a surrogate of congestion computed from haemoglobin and haematocrit), blood potassium, and estimated glomerular filtration rate during 2 months post-hospitalization for decompensated HF with reduced ejection fraction. METHODS AND RESULTS: The study was conducted in a single tertiary referral centre. Capillary blood samples were drawn by study nurses at home (7-12 am), and haematocrit, blood haemoglobin, creatinine, and potassium were measured using an approved home-based device (ABOTT i-STAT) (ClinicalTrials.gov: NCT01655134). Among the 15 home-monitored patients, two patients died (one suddenly), and one was readmitted for ischaemic acute pulmonary oedema, with a subsequent acute coronary syndrome, and did not have a complete 2-month follow-up. The 5-day-a-week biological home monitoring revealed an ePV >5.5 mL/g Hb, suggestive of undiagnosed residual congestion at discharge in 3 out the 15 patients. It was possible to document a number of episodes of hyperkalaemia (>5: mean ± standard deviation: 2.2 ± 2.2 or 5.5: 1.7 ± 1.6 mmol/L), hypokalaemia (<4: 1.9 ± 2.4 or 3.5: 0.5 ± 1.2 mmol/L), worsening renal function (drop in estimated glomerular filtration rate > 20%: 1.3 ± 1.8 or 30%: 0.7 ± 1.2) and recongestion (ePV rise above 10%: 1.4 ± 1.5, 15%: 2.3 ± 2.4, 5.5 mL/g Hb: 1.8 ± 2.6) episodes indicative of clinically relevant and potentially actionable cardiorenal and electrolytic patterns. CONCLUSIONS: Our findings demonstrate that a 5-day-a-week home monitoring combining haemoglobin/haematocrit, potassium, and creatinine measurements was able to capture a substantial number of clinically relevant cardiorenal and electrolyte events which are frequently overlooked and potentially actionable. Whether acting on these events may help optimizing renin angiotensin aldosterone system inhibitors and diuretic therapy warrants further dedicated testing. The ongoing HERMES HF study (NCT04050904) is assessing the short-term feasibility and safety of such a monitoring strategy, complemented by a decision support system, and generating recommendations based on ESC clinical guidelines in patients discharged after an episode of worsening heart failure with reduced ejection fraction.

Prognostic influence of acute decompensated heart failure in patients planned for transcatheter aortic valve implantation.

OBJECTIVE: The aim of our study was to evaluate the outcome of patients with severe aortic stenosis presenting with acute decompensated heart failure (ADHF) and planned for transcatheter aortic valve implantation (TAVI) and to study the variables influencing their prognosis. METHODS: Our retrospective study included 801 patients planned for TAVI in our center. Seven hundred and fifty-six underwent TAVI and were categorized according to ADHF as the initial clinical presentation into two groups: ADHF group (n = 261) and no-ADHF group (n = 495). Pre as well as periprocedural outcomes and 1 year mortality were analyzed. RESULTS: Among the patients planned for the TAVI procedure, 45 patients remained untreated: 35 patients died while waiting to undergo TAVI which represented 20% of all deaths in our study, ADHF was observed in 23 of 45 (51%) these untreated patients. The 1-year all-cause mortality rate was significantly higher in the ADHF group versus the no-ADHF group (27% vs. 15%, p < .0001). In multivariate analysis, male gender (odds ratio [OR] =2.5, 95% confidence interval [CI]: 1.37-4.57, p = .03), body mass index <25 kg/m2 (OR = 2.76, 95% CI: 1.51-5.04, p = .0009), and logistic EuroSCORE II ≥20% (OR = 3.04, 95% CI: 1.56-5.94, p = .001) were associated with a higher 1-year mortality in the ADHF group. CONCLUSION: The patients eligible for TAVI presenting with ADHF were associated with a higher mortality for both: while on the waiting list for TAVI as well as at 1-year follow-up and thus asking for clearer criteria to prioritize action in this high-risk TAVI patients.

Echocardiographic diastolic function evolution in patients with an anterior Q-wave myocardial infarction: insights from the REVE-2 study.

AIMS: Myocardial fibrosis plays a key role in the development of adverse left ventricular remodelling after myocardial infarction (MI). This study aimed to determine whether the circulating levels of BNP, collagen peptides, and galectin-3 are associated with diastolic function evolution (both deterioration and improvement) at 1 year after an anterior MI. METHODS AND RESULTS: The REVE-2 is a prospective multicentre study including 246 patients with a first anterior Q-wave MI. Echocardiographic assessment was performed at hospital discharge and ±1 year after MI. BNP, galectin-3, and collagen peptides were measured ±1 month after MI. Left ventricular diastolic dysfunction (DD) was defined according to the presence of at least two criteria of echocardiographic parameters: septal e' < 8 cm/s, lateral e' < 10 cm/s, and left atrial volume ≥ 34 mL/m2 . At baseline, 87 (35.4%) patients had normal diastolic function and 159 (64.6%) patients had DD. Follow-up of 61 patients among the 87 patients with normal diastolic function at baseline showed that 22 patients (36%) developed DD at 1 year post-MI. The circulating levels of amino-terminal propeptide of type III procollagen > 6 mg/L [odds ratio (OR) = 5.29; 95% confidence interval (CI) = 1.05-26.66; P = 0.044], galectin-3 > 13 µg/L (OR = 5.99; 95% CI = 1.18-30.45; P = 0.031), and BNP > 82 ng/L (OR = 10.25; 95% CI = 2.36-44.50; P = 0.002) quantified at 1 month post-MI were independently associated with 1 year DD. Follow-up of the 137 patients with DD at baseline among the 159 patients showed that 36 patients (26%) had a normalized diastolic function at 1 year post-MI. Patients with a BNP > 82 ng/L were less likely to improve diastolic function (OR = 0.06; 95% CI = 0.01-0.28; P = 0.0003). CONCLUSIONS: The present study suggests that circulating levels of amino-terminal propeptide of type III procollagen, galectin-3, and BNP may be independently associated with new-onset DD in post-MI patients.

Galectin-3 down-regulates antioxidant peroxiredoxin-4 in human cardiac fibroblasts: a new pathway to induce cardiac damage.

Galectin-3 (Gal-3) is increased in heart failure (HF) and promotes cardiac fibrosis and inflammation. We investigated whether Gal-3 modulates oxidative stress in human cardiac fibroblasts, in experimental animal models and in human aortic stenosis (AS). Using proteomics and immunodetection approaches, we have identified that Gal-3 down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. In parallel, Gal-3 increased peroxide, nitrotyrosine, malondialdehyde, and N-carboxymethyl-lysine levels and decreased total antioxidant capacity. Gal-3 decreased prohibitin-2 expression without modifying other mitochondrial proteins. Prx-4 silencing increased oxidative stress markers. In Gal-3-silenced cells and in heart from Gal-3 knockout mice, Prx-4 was increased and oxidative stress markers were decreased. Pharmacological inhibition of Gal-3 with modified citrus pectin restored cardiac Prx-4 as well as prohibitin-2 levels and improved oxidative status in spontaneously hypertensive rats. In serum from 87 patients with AS, Gal-3 negatively correlated with total antioxidant capacity and positively correlated with peroxide. In myocardial biopsies from 26 AS patients, Gal-3 up-regulation paralleled a decrease in Prx-4 and in prohibitin-2. Cardiac Gal-3 inversely correlated with Prx-4 levels in myocardial biopsies. These data suggest that Gal-3 decreased Prx-4 antioxidant system in cardiac fibroblasts, increasing oxidative stress. In pathological models presenting enhanced cardiac Gal-3, the decrease in Prx-4 expression paralleled increased oxidative stress. Gal-3 blockade restored Prx-4 expression and improved oxidative stress status. In AS, circulating levels of Gal-3 could reflect oxidative stress. The alteration of the balance between antioxidant systems and reactive oxygen species production could be a new pathogenic mechanism by which Gal-3 induces cardiac damage in HF.

A role for fumarate hydratase in mediating oxidative effects of galectin-3 in human cardiac fibroblasts.

AIMS: Galectin-3 (Gal-3), a ß-galactoside-binding lectin involved in cardiac inflammation and fibrosis, could regulate oxidative stress, although the mechanisms have not been elucidated. We herein investigated the changes in oxidative stress-related mediators induced by Gal-3 in human cardiac fibroblasts and in pathological animal and human models of cardiac diseases. RESULTS: Using quantitative proteomics and immunodetection approaches, we have identified that Gal-3 down-regulated fumarate hydratase (FH) in human cardiac fibroblasts. In parallel, Gal-3 increased fumarate production in a time-dependent manner. Gal-3 treatment enhanced carbonylated proteins detected through OxyBlot technique. Interestingly, treatment of cells with fumarate induced oxidative stress, enhanced fibroblast activation markers and increased collagen and interleukin-6 secretion. In Gal-3-silenced cells and in heart from Gal-3 knock-out mice, FH was increased and fumarate was decreased. In myocardial biopsies from patients with aortic stenosis (AS, n=26), FH levels were decreased as compared to Controls (n=13). Cardiac Gal-3 inversely correlated with FH levels in myocardial biopsies. In an experimental model of AS rats, pharmacological inhibition of Gal-3 restored cardiac FH, decreased fumarate concentration and improved oxidative status. CONCLUSION: In human cardiac fibroblasts, Gal-3 decreased FH expression increasing fumarate concentration and promoting oxidative stress. In human AS, cardiac levels of Gal-3 inversely associated with FH. Gal-3 blockade restored FH and improved fumarate and oxidative stress status in AS rats. FH is therefore a key molecule mediating Gal-3-induced oxidative stress in cardiac cells.

Association of digitalis treatment with outcomes following myocardial infarction in patients with heart failure or evidence of left ventricular dysfunction: an analysis from the High-Risk Myocardial Infarction Database Initiative.

BACKGROUND: Contradictory findings have been reported regarding the safety and efficacy of digitalis in patients recovering from acute myocardial infarction (MI). We studied the association of digitalis use with long-term and short-term prognosis in patients presenting with an acute MI complicated with heart failure (HF), left ventricular dysfunction, or both. METHODS AND RESULTS: Using the High-Risk MI Database Initiative combining data from 4 major clinical trials, totaling 27,673 patients, we investigated the association between digitalis use at baseline (3093 patients with digitalis and 24,580 without) with the rate of all-cause death, sudden cardiac death, cardiovascular death, HF hospitalization and the combination of the latter two, over a mean follow-up time of 2.7 years. Patients with and without atrial fibrillation (AF) were studied separately. After a propensity score-based analysis, among patients without AF, those receiving digitalis experienced a higher rate of all-cause [hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.42-1.67] and sudden cardiac death (HR 1.65, 95% CI 1.44-1.89), compared to those not receiving digitalis; similar results were found for the other 3 endpoints (all HR around 1.6). In contrast, in AF patients, digitalis had a milder effect on all outcomes (all HR ≤ 1.12), with significant association only for the composite endpoint (HR 1.10, 95% CI 1.00-1.21, p = 0.049); comparable results were obtained at 30 days. Finally, the detrimental effect associated with digitalis use appeared to be more pronounced in patients with ejection fraction ≥ 40%. CONCLUSIONS: In MI survivors with HF and/or systolic dysfunction, digitalis was associated with a significant increased risk of death in patients without AF with mild to neutral associations for patients with AF. These findings raise concerns regarding the safety of digitalis in MI survivors with HF, especially for those without AF.

Cardiac remodeling following reperfused acute myocardial infarction is linked to the concomitant evolution of vascular function as assessed by cardiovascular magnetic resonance.

BACKGROUND: Left ventricular (LV) remodeling following acute myocardial infarction (MI) is difficult to predict at an individual level although a possible interfering role of vascular function has yet to be considered to date. This study aimed to determine the extent to which this LV remodeling is influenced by the concomitant evolution of vascular function and LV loading conditions, as assessed by phase-contrast Cardiovascular Magnetic Resonance (CMR) of the ascending aorta. METHODS: CMR was performed in 121 patients, 2-4 days after reperfusion of a first ST-segment elevation myocardial infarction and 6 months thereafter. LV remodeling was: (i) assessed by the 6-month increase in end-diastolic volume (EDV) and/or ejection fraction (EF) and (ii) correlated with the indexed aortic stroke volume (mL.m-2), determined by a CMR phase-contrast sequence, along with derived functional vascular parameters (total peripheral vascular resistance (TPVR), total arterial compliance index, effective arterial elastance). RESULTS: At 6 months, most patients were under angiotensin enzyme converting inhibitors (86%) and beta-blockers (84%) and, on average, all functional vascular parameters were improved whereas blood pressure levels were not. An increase in EDV only (EDV+/EF-) was documented in 17% of patients at 6 months, in EF only (EDV-/EF+) in 31%, in both EDV and EF (EDV+/EF+) in 12% and neither EDV nor EF (EDV-/EF-) in 40%. The increase in EF was mainly and independently linked to a concomitant decline in TPVR (6-month change in mmHg.min.m2.L-1, EDV-/EF-: +1 ± 8, EDV+/EF-: +3 ± 9, EDV-/EF+: -7 ± 6, EDV+/EF+: -15 ± 20, p < 0.001) while the absence of any EF improvement was associated with high persisting rates of abnormally high TPVR at 6 months (EDV-/EF-: 31%, EDV+/EF-: 38%, EDV-/EF+: 5%, EDV+/EF+: 13%, p = 0.007). By contrast, the 6-month increase in EDV was mainly dependent on cardiac as opposed to vascular parameters and particularly on the presence of microvascular obstruction at baseline (EDV-/EF-: 37%, EDV+/EF-: 76%, EDV-/EF+: 38%, EDV+/EF+: 73%, p = 0.003). CONCLUSION: LV remodeling following reperfused MI is strongly influenced by the variable decrease in systemic vascular resistance under standard care vasodilating medication. The CMR monitoring of vascular resistance may help to tailor these medications for improving vascular resistance and consequently, LV ejection fraction. TRIAL REGISTRATION: NCT01109225 on ClinicalTrials.gov site (April, 2010).

Impact of eplerenone on cardiovascular outcomes in heart failure patients with hypokalaemia.

AIMS: Although hypokalaemia is common among patients with heart failure (HF), the prognostic significance of baseline hypokalaemia and hypokalaemia during follow-up in HF patients receiving a mineralocorticoid receptor antagonist (MRA) remains uncertain. METHODS AND RESULTS: Results of the EMPHASIS-HF trial in patients (n = 2737) with HF and reduced EF with mild symptoms, randomized to eplerenone or placebo, were analysed with regard to the presence or occurrence of hypokalaemia (serum K+ <4.0 mmol/L) and the risk of cardiovascular death or hospitalization for HF (primary endpoint). Median follow-up was 21 months. Baseline hypokalaemia and hypokalaemia during follow-up were common occurrences (19.6% and 40.6%, respectively). Hypokalaemia during follow-up was associated with worse outcomes in multivariable analyses [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.05-1.52, P = 0.01] without evidence of interaction with eplerenone. In contrast, baseline hypokalaemia was associated with outcomes in the placebo group (HR 1.37, 95% CI 1.05-1.79, P = 0.02) but not in the eplerenone group (HR 0.87, 95% CI 0.62-1.23, P = 0.44; P for interaction = 0.04). Concurrently, eplerenone was found to be more protective in patients with baseline hypokalaemia vs. patients without baseline hypokalaemia compared with placebo (HR 0.44, 95% 0.30-0.64, P < 0.0001 vs. 0.69, 95% CI 0.57-0.83, P = 0.0001; P for interaction = 0.04). In patients without baseline hypokalaemia, eplerenone use decreased the rate of hypokalaemia during follow-up (HR 0.69, 95% CI 0.59-0.80, P < 0.001). A potassium level >4.0 mmol/L at 1 month after randomization mediated 26.0% (0.6-51.4%) of the eplerenone treatment effect (P = 0.04). CONCLUSION: In HF patients receiving optimal therapy but not treated with eplerenone, baseline hypokalaemia was associated with worse outcomes. Conversely, hypokalaemia amplified the treatment effect of eplerenone.

Prognostic Value of the Thrombolysis in Myocardial Infarction Risk Score in ST-Elevation Myocardial Infarction Patients With Left Ventricular Dysfunction (from the EPHESUS Trial).

The Thrombolysis in Myocardial Infarction (TIMI) risk score remains a robust prediction tool for short-term and midterm outcome in the patients with ST-elevation myocardial infarction (STEMI). However, the validity of this risk score in patients with STEMI with reduced left ventricular ejection fraction (LVEF) remains unclear. A total of 2,854 patients with STEMI with early coronary revascularization participating in the randomized EPHESUS (Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial were analyzed. TIMI risk score was calculated at baseline, and its predictive value was evaluated using C-indexes from Cox models. The increase in reclassification of other variables in addition to TIMI score was assessed using the net reclassification index. TIMI risk score had a poor predictive accuracy for all-cause mortality (C-index values at 30 days and 1 year ≤0.67) and recurrent myocardial infarction (MI; C-index values ≤0.60). Among TIMI score items, diabetes/hypertension/angina, heart rate >100 beats/min, and systolic blood pressure <100 mm Hg were inconsistently associated with survival, whereas none of the TIMI score items, aside from age, were significantly associated with MI recurrence. Using a constructed predictive model, lower LVEF, lower estimated glomerular filtration rate (eGFR), and previous MI were significantly associated with all-cause mortality. The predictive accuracy of this model, which included LVEF and eGFR, was fair for both 30-day and 1-year all-cause mortality (C-index values ranging from 0.71 to 0.75). In conclusion, TIMI risk score demonstrates poor discrimination in predicting mortality or recurrent MI in patients with STEMI with reduced LVEF. LVEF and eGFR are major factors that should not be ignored by predictive risk scores in this population.

Grey-Matter Metabolism in Relation with White-Matter Lesions in Older Hypertensive Patients with Subjective Memory Complaints: A Pilot Voxel-Based Analysis Study.

BACKGROUND: This study aimed at assessing the changes in brain metabolism related to white-matter magnetic resonance (MR) hyperintensities of presumed vascular origin, with a voxel-based quantitative analysis of (18F)-fluorodesoxyglucose positron emission tomography (FDG-PET) imaging. METHODS: Sixty older hypertensive patients with subjective memory complaints (75 ± 5 years, 34 women) were prospectively referred to FDG-PET and MRI brain imaging. The Statistical Parametric Mapping software was used to assess the correlation between brain distribution of FDG and white-matter hyperintensities assessed by the Fazekas score on MRI images. RESULTS: The Fazekas score was inversely related to FDG uptake, independently of age and gender, within 14 Brodmann areas located mainly in the frontal lobe but also in certain limbic, insular and temporal areas. This relationship was also found to be largely independent of the volume of grey matter expressed in percentage of cranial volume, an index of atrophy. CONCLUSIONS: White-matter MR hyperintensities of presumed vascular origin are cross-sectionally associated with a lower grey-matter metabolism, mainly but not only within frontal areas and independently of age, gender and grey-matter atrophy.

Beneficial Effects of Norepinephrine Alone on Cardiovascular Function and Tissue Oxygenation in a Pig Model of Cardiogenic Shock.

INTRODUCTION: The present study was developed to investigate the effects of norepinephrine alone on hemodynamics and intrinsic cardiac function in a pig model of cardiogenic shock mimicking the clinical setting. METHODS: Cardiogenic shock was induced by 1-h ligation of the left anterior descending (LAD) artery followed by reperfusion. Pigs were monitored with a Swan-Ganz catheter, a transpulmonary thermodilution catheter, and a conductance catheter placed in the left ventricle for pressure-loop measurements. Measurements were performed before LAD occlusion, 1 h after LAD occlusion, and 4 h after myocardial reperfusion. RESULTS: Myocardial infarction and reperfusion was followed by cardiogenic shock characterized by a significant increase in heart rate and significant decreases in mean arterial pressure (MAP), mixed venous oxygen saturation (SVO2), left ventricular end-diastolic pressure (LVEDP), prerecruitable stroke work (PRSW), and cardiac power index (CPI). Lactate levels were significantly increased. The systemic vascular resistance index (SVRI) and global end-diastolic volume index (GEDVI) remained unchanged. When compared with the control group (n = 6), norepinephrine infusion (n = 6) was associated with no changes in heart rate, a significant increase in MAP, SVO2, left ventricular ejection fraction, pressure development during isovolumic contraction, SVRI, and CPI and a decrease in lactate level. Cardiac index tended to increase (P = 0.059), whereas PRSW did not change in the norepinephrine group. LVEDP and GEDVI remained unchanged. CONCLUSIONS: Norepinephrine alone is able to improve hemodynamics, cardiac function, and tissue oxygenation in a pig model of ischemic cardiogenic shock.

Temporal epilepsy lesions may be detected by the voxel-based quantitative analysis of brain FDG-PET images using an original block-matching normalization software.

INTRODUCTION: Statistical parametric mapping (SPM) provides useful voxel-by-voxel analyses of brain images from (18)F-fluorodesoxyglucose positron emission tomography (FDG-PET) after an initial step of spatial normalization through an anatomical template model. In the setting of the preoperative workup of patients with temporal epilepsy, this study aimed at assessing a block-matching (BM) normalization method, where most transformations are computed through small blocks, a principle that minimizes artefacts and overcomes additional image-filtering. METHODS: Brain FDG-PET images from 31 patients with well-characterised temporal lobe epilepsy and among whom 22 had common mesial temporal lobe epilepsy were retrospectively analysed using both BM and conventional SPM normalization methods and with PET images from age-adjusted controls. Different threshold p values corrected for cluster volume were considered (0.01, 0.005, and 0.001). RESULTS: The use of BM provided equivalent values to those of SPM with regard to the overall volumes of temporal and extra-temporal hypometabolism, as well as similar sensitivity for detecting the involved temporal lobe, reaching 87 and 94 % for SPM and BM, respectively, at a threshold p value of 0.01. However, the ability to more accurately localize brain lesions within the mesial portion of the temporal lobe was a little higher with BM than with SPM with respective sensitivities reaching 78 % for BM and 45 % for SPM (p < 0.05). CONCLUSIONS: BM normalization compares well with conventional SPM for the voxel-based quantitative analysis of the FDG-PET images from temporal epilepsy patients. Further studies in different population are needed to determine whether BM is truly an accurate alternative to SPM in this setting.

Comprehensive monitoring of cardiac remodeling with aortic stroke volume values provided by a phase-contrast MRI sequence.

OBJECTIVES: Blood pressure (BP) and its changes with antihypertensive therapy are key parameters when monitoring left ventricular (LV) remodeling. This dual cross-sectional and longitudinal MRI study aimed to determine whether this monitoring is enhanced by aortic stroke volume (SV) values provided by a phase-contrast sequence. METHODS: The study involved 334 MRI examinations from 247 study participants who had no significant cardiac disease (18-85 years old, 40% with hypertension) and among whom 48 had a 2-4-year MRI follow-up. Left ventricular hypertrophy and concentric geometry were: respectively assessed according to LV mass indexed to body surface area (g/m) and mass/end-diastolic volume ratio (concentric remodeling index); and correlated with vascular parameters involving BP and the indexed SV (ml/m) determined in the ascending aorta with a phase-contrast sequence. RESULTS: Stroke volume was highly variable, ranging from 22 to 74 ml/m. The best cross-sectional correlates were: mean BP × SV product, reflecting cardiac work, for LV mass (r = 0.21); and mean BP/SV ratio, reflecting arterial load, for concentric geometry (r = 0.29). These two SV-derived parameters led to more than two-fold enhancements in cross-sectional predictions compared with BP parameters alone, whereas their longitudinal changes over time paralleled those of concentric geometry (P = 0.003 for mean BP/SV) and LV mass (P = 0.006 for mean BP × SV), suggesting direct links with cardiac remodeling. CONCLUSION: The determination of aortic SV with a phase-contrast sequence leads to a significant enhancement in the characterization and monitoring of cardiac remodeling.

Predictive factors of brain death in severe stroke patients identified by organ procurement and transplant coordination in Lorrain, France.

There are no established predictive factors to identify patients at the acute phase of severe stroke with a high probability of presenting brain death (BD). We retrospectively collected clinical and paraclinical data of consecutive patients at the acute phase of severe stroke with a potential progression to BD through the hospital organ procurement and transplant coordination system in five centres in Lorrain (France) between 1 January 2012 and 31 December 2013. Final endpoint was adjudicated BD. Of 400 included patients, 91 (23%) presented adjudicated BD. Initial Glasgow Coma Scale score ≤6 (P = 0.008), herniation (P = 0.009), hydrocephalus (P = 0.019), initial systolic blood pressure >150 mmHg (P = 0.002), past history of alcohol abuse (P = 0.019) and stroke volume >65 ml (P = 0.040) were significantly associated with BD progression. Two prognostic scores for stroke with unquantifiable or quantifiable volume were built according to the number of risk factors presented. Following internal validation, the respective bias-corrected predictive performance (c-index) of the two scores was 72% (95% confidence interval: 67-78%) and 77% (95% confidence interval: 72-82%). These scores could form the basis of a simple tool of six criteria to help physicians make the difficult decision of intensive care unit management to preserve organs in potential donors.

Prolonged prone positioning under VV-ECMO is safe and improves oxygenation and respiratory compliance.

BACKGROUND: Data are sparse regarding the effects of prolonged prone positioning (PP) during VV-ECMO. Previous studies, using short sessions (<12 h), failed to find any effects on respiratory system compliance. In the present analysis, the effects of prolonged PP sessions (24 h) were retrospectively studied with regard to safety data, oxygenation and respiratory system compliance. METHODS: Retrospective review of 17 consecutive patients who required both VV-ECMO and prone positioning. PP under VV-ECMO was considered when the patient presented at least one unsuccessful ECMO weaning attempt after day 7 or refractory hypoxemia combined or not with persistent high plateau pressure. PP sessions had a duration of 24 h with fixed ECMO and respiratory settings. PP was not performed in patients under vasopressor treatment and in cases of recent open chest cardiac surgery. RESULTS: Despite optimized protective mechanical ventilation and other adjuvant treatment (i.e. PP, inhaled nitric oxide, recruitment maneuvers), 44 patients received VV-ECMO during the study period for refractory acute respiratory distress syndrome. Global survival rate was 66 %. Among the latter, 17 patients underwent PP during VV-ECMO for a total of 27 sessions. After 24 h in prone position, PaO2/FiO2 ratio significantly increased from 111 (84-128) to 173 (120-203) mmHg (p < 0.0001) while respiratory system compliance increased from 18 (12-36) to 32 (15-36) ml/cmH2O (p < 0.0001). Twenty-four hours after the return to supine position, tidal volume was increased from 3.0 (2.2-4.0) to 3.7 (2.8-5.0) ml/kg (p < 0.005). PaO2/FiO2 ratio increased by over 20 % in 14/14 sessions for late sessions (≥7 days) and in 7/13 sessions for early sessions (<7 days) (p = 0.01). Quantitative CT scan revealed a high percentage of non-aerated or poorly-aerated lung parenchyma [52 % (41-62)] in all patients. No correlation was found between CT scan data and respiratory parameter changes. Hemodynamics did not vary and side effects were rare (one membrane thrombosis and one drop in ECMO blood flow). CONCLUSION: When used in combination with VV-ECMO, 24 h of prone positioning improves both oxygenation and respiratory system compliance. Moreover, our study confirms the absence of serious adverse events.