Jordi Bañeras

Use of perampanel in one case of super-refractory hypoxic myoclonic status: Case report

Proper treatment of hypoxic myoclonic status is not clearly determined. Induced hypothermia is improving prognosis and a more aggressive treatment might be beneficial in some patients. Among the new options of antiepileptic drugs, perampanel (PER) is a drug with a novel mechanism, and it might be a promising drug for myoclonic status or as an antimyoclonic drug. We describe the use of PER in one patient with hypoxic super-refractory myoclonic status. Description A 51-year-old patient presented after an out-of-hospital cardiac arrest due to an acute myocardial infarction. The patient was diagnosed with clinical and electrical (EEG) myoclonic status at the rewarming phase. Several treatments were used, starting with clonazepam, valproate, sedation (midazolam, propofol), and subsequently barbiturate-induced coma with persistent myoclonic status. Finally, we decided to try PER (dose: 6–8 mg) through a nasogastric tube, resulting in a marked improvement of EEG activity and myoclonus decrease. The patient had a progressive clinical improvement, with a CPC (Cerebral Performance Category) scale score of 1. Conclusion This case shows the potential utility of PER as a therapeutic option in super-refractory hypoxic status and even its potential use before other aggressive alternatives considering their greater morbidity.

Obesity induced by high fat diet attenuates postinfarct myocardial remodeling and dysfunction in adult B6D2F1 mice

Obesity is a major risk factor for cardiovascular morbidity and mortality. However, some studies suggest that among patients with established cardiovascular disease, obesity is associated with better prognosis, a phenomenon described as the obesity paradox. In this study we tested the hypothesis that obesity with hyperinsulinemia and without hyperglycemia attenuates the impact of transient coronary occlusion on left ventricular remodeling and function. B6D2F1 mice from both genders fed with a high fat diet (HFD) or control diet for 6 months were subjected to 45 min of coronary occlusion and 28 days of reperfusion. Left ventricular dimensions and function were assessed by serial echocardiography, and infarct size was determined by Picrosirius red staining. HFD mice developed obesity with hypercholesterolemia and hyperinsulinemia in the absence of hyperglycemia or hypertension. During the period of feeding, no changes were observed in ventricular mass, volume or function, or in vascular reactivity. HFD attenuated the consequences of transient coronary occlusion as shown by a marked reduction in infarct size (51%, P = 0.021) and cardiac dilation, as well as improved left ventricular function as compared to control diet animals. These effects were associated with enhanced reperfusion injury salvage kinases (RISK) pathway function in HFD hearts shown as increased Akt and GSK3β phosphorylation. These results demonstrate that dietary obesity without hyperglycemia or hypertension attenuates the impact of ischemia/reperfusion injury in association with increased insulin signaling and RISK activation. This study provides experimental support to the controversial concept of the obesity paradox in humans.

Increased von Willebrand factor, P-selectin and fibrin content in occlusive thrombus resistant to lytic therapy

Therapeutic fibrinolysis is ineffective in 40 % of ST-segment elevation acute myocardial infarction (STEMI) patients, but understanding of the mechanisms is incomplete. It was our aim to compare the composition of coronary thrombus in lysis-resistant STEMI patients with that of lysis-sensitive patients. Intracoronary thrombi (n=64) were obtained by aspiration in consecutive STEMI patients. Of them, 20 had received fibrinolysis and underwent rescue percutaneous coronary intervention (r-PCI, lysis-resistant patients) and 44 underwent primary PCI (p-PCI). Lysis-sensitivity was determined in vitro by clot permeability measurements and turbidimetric lysis in plasma of 44 patients undergoing p-PCI and 20 healthy donors. Clot-lysis sensitivity was defined as a clot-lysis time not greater than 1 SD over the mean of healthy donors. Coronary thrombus composition in 20 lysis-resistant and in 20 lysis-sensitive patients was analysed by immunofluorescence with confocal microscopy. Plasma biomarkers (P-selectin, VWF, PAI-1, t-PA, D-dimer, TF pathway markers, plasmin and CD34+) were measured simultaneously on peripheral blood. Lysis-resistant clots had higher levels of fibrin (p=0.02), P-selectin (p=0.03) and VWF (p=0.01) than lysis-sensitive clots. Among thrombi obtained ≤ 6 hours after onset of symptoms, those from lysis-resistant patients showed a higher content in fibrin than those from p-PCI patients (p=0.01). Plasma PAI-1 (p=0.02) and D-dimer levels were significantly higher (p=0.003) in lysis-resistant patients, whereas plasmin levels were lower (p=0.03). Multivariate analysis showed the content of fibrin and VWF within thrombus as predictors of thrombolysis resistance. In conclusion, coronary thrombi in STEMI patients resistant to fibrinolysis are characterised by higher fibrin, P-selectin and VWF content than lysis-sensitive thrombi.

Predictors of Moderate-to-Severe Pericardial Effusion, Cardiac Tamponade, and Electromechanical Dissociation in Patients With ST-Elevation Myocardial Infarction

Occurrence of moderate-to-severe pericardial effusion (PE; ≥10 mm), cardiac tamponade (CT), and sudden electromechanical dissociation (EMD) was investigated in 4,361 patients with ST-elevation myocardial infarction from 1993 to 2011 in 3 different periods: 1993 to 2000 (n: 1,488); 2001 to 2008 (n: 1,844); and 2009 to 2011 (n: 1,014). Their predictors, including the use of no reperfusion therapy (n: 1,186), thrombolysis (n: 1,607), or primary percutaneous coronary intervention (PPCI, n: 1,562), were also evaluated. Incidence of PE (8.7%, 6.8%, and 5.0%), CT (5.0%, 2.9%, and 1.9%), and EMD (3.7%, 1.7%, and 1.0%), declined over the 3 periods as did mortality (12.0% 8.2%, and 5.9%) with different rates of thrombolytic therapy (52%, 37%, and 14%) and PPCI (7%, 38%, and 76%; all p<0.001). In patients treated without reperfusion therapy, thrombolysis, and PPCI, incidence of PE (12.0%, 5.7%, and 4.3%), CT (6.0%, 3.0%, and 2.2%), and EMD (4.1%, 2.2%, and 0.8%) was different as was mortality (14.4%, 8.3%, and 5.9%; all p<0.001). Independent predictors of PE were lateral infarction (odds ratio [OR] 4.09, 95% confidence interval [CI] 2.57 to 6.49), increasing age (OR 1.05, 95% CI 1.04 to 1.07), number of electrocardiographic leads involved (OR 1.34, 95% CI 1.23 to 1.45), and admission delay (OR 1.01, 95% CI 1.01 to 1.02). Increasing ejection fraction (OR 0.97, 95% CI 0.96 to 0.98), thrombolysis (OR 0.53, 95% CI 0.37 to 0.75), and PPCI (OR 0.35, 95% CI 0.25 to 0.50), however, were protectors (all p<0.001). Lateral infarction, age, number of leads involved, ejection fraction, thrombolytic therapy, and PPCI were also predictors/protectors of CT and EMD. In conclusion, PE, CT, and EMD rates in patients with ST-elevation myocardial infarction have objectively fallen in the last 2 decades, and their predictors are lateral site, increasing age, number of leads involved, and lack of reperfusion therapy. Late hospital admission is also a relevant predictor of PE.

Hospital and 4-Year Mortality Predictors in Patients With Acute Pulmonary Edema With and Without Coronary Artery Disease.

Background Long‐term prognosis of acute pulmonary edema (APE) remains ill defined. Methods and Results We evaluated demographic, echocardiographic, and angiographic data of 806 consecutive patients with APE with (CAD) and without coronary artery disease (non‐CAD) admitted from 2000 to 2010. Differences between hospital and long‐term mortality and its predictors were also assessed. CAD patients (n=638) were older and had higher incidence of diabetes and peripheral vascular disease than non‐CAD (n=168), and lower ejection fraction. Hospital mortality was similar in both groups (26.5% vs 31.5%; P=0.169) but APE recurrence was higher in CAD patients (17.3% vs 6.5%; P<0.001). Age, admission systolic blood pressure, recurrence of APE, and need for inotropics or endotracheal intubation were the main independent predictors of hospital mortality. In contrast, overall mortality (70.0% vs 57.1%; P=0.002) and readmission for nonfatal heart failure after a 45‐month follow‐up (10–140; 17.3% vs 7.6%; P=0.009) were higher in CAD than in non‐CAD patients. Age, peripheral vascular disease, and peak creatine kinase MB during index hospitalization, but not ejection fraction, were the main independent predictors of overall mortality, whereas coronary revascularization or valvular surgery were protective. These interventions were mostly performed during hospitalization index (294 of 307; 96%) and not intervened patients showed a higher risk profile. Conclusions Long‐term mortality in APE is high and higher in CAD than in non‐CAD patients. Considering the different in‐hospital and long‐term mortality predictors herein described, which do not necessarily involve systolic function, it is conceivable that a more aggressive interventional program might improve survival in high‐risk patients.

Area at risk and collateral circulation in a first acute myocardial infarction with occluded culprit artery. STEMI vs non-STEMI patients

BACKGROUND It is unclear why among patients with first acute myocardial infarction and an occluded culprit artery only some present ST segment elevation. In fact, there is no study that compares the angiographic area at risk and the collateral circulation in first NSTEMI vs STEMI patients. METHODS AND RESULTS 205 patients admitted for myocardial infarction with occluded culprit artery were included, 132 STEMI and 73 NSTEMI. Demographic data, the area at risk determined by the BARI score and collateral supply by the Rentrop score from the 2 groups were compared. NSTEMI patients showed lower peak Tn I than STEMI in the overall group but also in the 3 subsets with different culprit arteries (p < .001). They also presented a higher rate of left circumflex coronary artery (CFX) as culprit artery (52% vs 14%, p < .001), smaller BARI score area of the culprit artery (5.4 vs 7.6, p < .001), and higher frequency of well-developed collaterals (Rentrop score ≥ 2, 1.82 vs 0.41, p < .001). The latter was also higher in each of the 3 different culprit arteries (p = .002-<0.001) Among 38 NSTEMI patients with CFX occlusion, 20 with ≥1 mm ST depression in V2 to V4 (possible posterior infarction) showed a similar Rentrop score than the 18 with other ECG changes but lower Tn I peak (p = .012). CONCLUSIONS In first acute myocardial infarction with an occluded culprit artery NSTEMI patients - including those with possible posterior infarction - present smaller infarct size and higher collateral blood supply than STEMI patients in each of the 3 main culprit arteries.

Non-obstructive prosthetic heart valve thrombosis (NOPVT): Really a benign entity?

AIMS To assess the effectiveness of different treatment strategies in patients with non-obstructive prosthetic valve thrombosis (NOPVT) during hospitalization and long-term follow-up. METHODS NOPVT was diagnosed by transesophageal echocardiography. Resolution was defined as the disappearance or reduction of the thrombus under anticoagulation. All cases were first managed with optimization of anticoagulation. At discharge, patients received oral anticoagulation (OAC) alone or OAC and antiplatelet therapy (double treatment). Adverse events were defined as cardiovascular death, recurrence, thromboembolic events or major bleeding. RESULTS From 1997 to 2012, 47 patients (mean age: 65years; women: 60%) were diagnosed with NOPVT (mitral valve: 97%). Previous poor anticoagulation control was documented in 66% of patients. Twenty-one patients (45%) were treated with unfractionated heparin (UFH), especially those with thrombus size >10mm (19/21). Optimization of OAC was performed in the remaining patients. Treatment failed in 13 (27.6%) patients, mostly in those who received UFH (10/13), requiring surgery (53.8%) or fibrinolysis (30.7%). Forty-two patients survived and, at discharge, 44% of patients received OAC alone and 56% the double treatment. At follow-up (median 23months; range 0.03-116months), 59.5% of patients presented cardiovascular events, however no differences in outcome were observed with double treatment or OAC alone (p=0.385). CONCLUSIONS NOPVT is a high-risk complication, not only during hospitalization but also during follow-up. Optimization of anticoagulation is efficient in most patients except in thrombi ≥10mm treated with UFH. The double treatment does not prevent adverse events or complications during follow-up.

Short-term exposure to air pollutants increases the risk of ST elevation myocardial infarction and of infarct-related ventricular arrhythmias and mortality

BACKGROUND The relation between STEMI and air pollution (AP) is scant. We aimed to investigate the short term association between AP and the incidence of STEMI, and STEMI-related ventricular arrhythmias (VA) and mortality. METHODS The study was carried out in the area of Barcelona from January 2010 to December 2011. Daily STEMI rates and incidence of STEMI-related VA and mortality were obtained prospectively. The corresponding daily levels of the main pollutants were recorded as well as the atmospheric variables. Three cohorts were defined in order to minimize exposure bias. The magnitude of association was estimated using a time-series design and was adjusted according to atmospheric variables. RESULTS The daily rate of hospital admissions for STEMI was associated with increases in PM 2.5, PM 10, lead and NO2 concentrations. VA incidence and mortality were associated with increases in PM 2.5 and PM 10 concentrations. In the most specific cohort, BCN (Barcelona) Attended & Resident, STEMI incidence was associated with increases in PM 2.5 (1.009% per 10μg/m3) and PM 10 concentrations (1.005% per 10μg/m3). VA was associated with increases in PM 2.5 (1.021%) and PM 10 (1.015%) and mortality was associated with increases in PM 2.5 (1.083%) and PM 10 (1.045%). CONCLUSIONS Short-term exposure to high levels of PM 2.5 and PM 10 is associated with increased daily STEMI admissions and STEMI-related VA and mortality. Exposure to high levels of lead and NO2 is associated with increased daily STEMI admissions, and NO2 with higher mortality in STEMI patients.

Cardiac tamponade and adrenal insufficiency due to pembrolizumab: a case report

Abstract Introduction Patients who receive or have received anti-programmed cell-death-1 (PD-1) monoclonal antibodies can develop immune-related adverse events due to activation of the immune system. Case presentation We report a case of a patient who received pembrolizumab and presented with cardiac tamponade. Despite pericardial drainage, she persisted with refractory arterial hypotension due to secondary adrenal insufficiency. After initiating corticosteroid therapy, the patient recovered successfully. Discussion The association of pericarditis, hypophysitis and thyroid dysfunction support the diagnosis of a life-threatening immune-related adverse event due to pembrolizumab. In case of immune-related adverse events secondary to anti-PD-1 monoclonal antibodies, corticosteroid therapy should be promptly initiated in order to avoid major complications.

Therapeutic Hypothermia, Propofol, and High Lactate Levels: A Suspicious Combination

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