Dorota Sobczyk

Vernakalant hydrochloride for the rapid conversion of atrial fibrillation after cardiac surgery a randomized, double-blind, placebo-controlled trial

Background—Postoperative atrial arrhythmias are common and are associated with considerable morbidity. This study was designed to evaluate the efficacy and safety of vernakalant for the conversion of atrial fibrillation (AF) or atrial flutter (AFL) after cardiac surgery. Methods and Results—This was a prospective, randomized, double-blind, placebo-controlled trial of vernakalant for the conversion of AF or AFL after coronary artery bypass graft, valvular surgery, or both. Patients were randomly assigned 2:1 to receive a 10-minute infusion of 3 mg/kg vernakalant or placebo. If AF or AFL was present after a 15-minute observation period, then a second 10-minute infusion of 2 mg/kg vernakalant or placebo was given. The primary end point was the conversion of postcardiac surgery AF or AFL to sinus rhythm within 90 minutes of dosing. In patients with AF, 47 of 100 (47%) who received vernakalant converted to SR compared with 7 of 50 (14%) patients who received placebo (P<0.001). The median time to conversion was 12 minutes. Vernakalant was not effective in converting postoperative AFL to sinus rhythm. Two serious adverse events occurred within 24 hours of vernakalant administration (hypotension and complete atrioventricular block). There were no cases of torsades de pointes, sustained ventricular tachycardia, or ventricular fibrillation. There were no deaths. Conclusions—Vernakalant was safe and effective in the rapid conversion of AF to sinus rhythm in patients who had AF after cardiac surgery. Clinical Trial Registration—clinicaltrials.gov. Identifier: NCT00125320.

Bedside Ultrasonographic Measurement of the Inferior Vena Cava Fails to Predict Fluid Responsiveness in the First 6 Hours After Cardiac Surgery: A Prospective Case Series Observational Study

OBJECTIVE To assess validity of respiratory variation of inferior vena cava (IVC) diameter to predict fluid responsiveness and guide fluid therapy in mechanically ventilated patients during the first 6 hours after elective cardiac surgery. DESIGN Prospective observational case series study. SETTING Single-center hospital. PATIENTS 50 consecutive patients undergoing elective cardiac surgery. INTERVENTIONS Transthoracic bedside echocardiography. MEASUREMENTS AND MAIN RESULTS Parameters derived from ultrasonographic assessment of the IVC diameter (collapsibility index [CI], distensibility index [DI], and IVC/aorta index). In the whole study group, change in fluid balance correlated with change in IVC maximum diameter (p = 0.034, r = 0.176). IVC-CI and IVC-DI correlated with IVC/aorta index. A weak correlation between central venous pressure (CVP) and IVC-derived parameters (IVC-CI and IVC-DI) was noticed. Despite statistical significance (p<0.05), all observed correlations expressed low statistical power (r<0.21). There were no statistically significant differences between fluid responders and nonresponders in relation to clinical parameters, CVP, ultrasound IVC measurement, and IVC-derived indices. CONCLUSION Dynamic IVC-derived parameters (IVC-CI, IVC-DI, and IVC/aorta index) and CVP are not reliable predictors of fluid responsiveness in the first 6 hours after cardiac surgery. Complexity of physiologic factors modulating cardiac performance in this group may be responsible for the difficulty in finding a plausible monitoring tool for fluid guidance. Bedside ultrasonographic measurement of IVC is unable to predict fluid responsiveness in the first 6 hours after cardiac surgery.

Lipoprotein-associated phospholipase A2 is elevated in patients with severe aortic valve stenosis without clinically overt atherosclerosis.

Abstract Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory mediator involved in atherosclerosis. Since aortic valve stenosis (AVS) is regarded as an atherosclerosis-like inflammatory disease, we sought to investigate whether AVS is associated with elevated Lp-PLA2. Methods: Plasma Lp-PLA2 levels were determined in 48 consecutive patients with severe AVS without atherosclerotic vascular disease and compared with the values obtained in 48 controls matched for age, sex and cardiovascular risk factors. Results: Lp-PLA2 was higher in AVS than in controls (242.3±50.4 vs. 151.9±28.1 ng/mL, p<0.0001). Lp-PLA2 correlated inversely with aortic valve area (AVA) (r=–0.53; p=0.0001) and positively with mean pressure gradient (PG) (r=0.32; p=0.029). In multivariable analysis C-reactive protein (CRP) (OR=1.42; 95% CI 0.95–2.1; p=0.09) and AVA (OR=0.003; 95% CI 0.00004–0.23; p<0.01) were independently associated with Lp-PLA2 above a mean of 242 ng/mL. After adjustment for CRP, AVA was the only independent predictor of Lp-PLA2 in AVS patients (p<0.001). Conclusions: This study is the first to show that AVS is characterized by increased plasma Lp-PLA2 levels associated with the severity of AVS, which suggests active involvement of Lp-PLA2 in the pathogenesis of AVS.

Does diabetes accelerate the progression of aortic stenosis through enhanced inflammatory response within aortic valves

Diabetes predisposes to aortic stenosis (AS). We aimed to investigate if diabetes affects the expression of selected coagulation proteins and inflammatory markers in AS valves. Twenty patients with severe AS and concomitant type 2 diabetes mellitus (DM) and 40 well-matched patients without DM scheduled for valve replacement were recruited. Valvular tissue factor (TF), TF pathway inhibitor (TFPI), prothrombin, C-reactive protein (CRP) expression were evaluated by immunostaining and TF, prothrombin, and CRP transcripts were analyzed by real-time PCR. DM patients had elevated plasma CRP (9.2 [0.74–51.9] mg/l vs. 4.7 [0.59–23.14] mg/l, p = 0.009) and TF (293.06 [192.32–386.12] pg/ml vs. 140 [104.17–177.76] pg/ml, p = 0.003) compared to non-DM patients. In DM group, TF−, TFPI−, and prothrombin expression within valves was not related to demographics, body mass index, and concomitant diseases, whereas increased expression related to DM was found for CRP on both protein (2.87 [0.5–9]% vs. 0.94 [0–4]%, p = 0.01) and transcript levels (1.3 ± 0.61 vs. 0.22 ± 0.43, p = 0.009). CRP-positive areas were positively correlated with mRNA TF (r = 0.84, p = 0.036). Diabetes mellitus is associated with enhanced inflammation within AS valves, measured by CRP expression, which may contribute to faster AS progression.

Feasibility and accuracy of bedside transthoracic echocardiography in diagnosis of acute proximal aortic dissection

Study objectiveThe purpose of the present study was to establish the accuracy of transthoracic echocardiography (TTE) in diagnosis of acute type A aortic dissection in comparison to computed tomography (CT), with reference to the intraoperative image.MethodsThe retrospective analysis included 178 patients referred to the cardiac surgery unit in our center due to acute type A dissection between 01-01-2008 and 31-12-2013, who underwent both TTE and CT. Intraoperative image was considered as a reference.ResultsStatistical analysis did not show any significant differences between computed tomography and echocardiography in the detection of the proximal aortic dissection. In patients with aortic valve abnormalities, procedure of choice was replacement by a composite graft (77,59%), whereas patients with a normal image of aortic valve were more likely to have the valve sparing procedure (50,88%). The R-Spearman statistics shows a strong positive correlation between maximum diameter of ascending aorta measured by TTE and CT (cc 0.869) and TTE and intraoperative measurement (cc 0.844).ConclusionOur data confirm that transthoracic echocardiography is a reliable method for diagnosis of proximal aortic dissection. TTE provides a reliable value of maximum diameter of the ascending aorta in comparison to both CT and direct intraoperative measurement. Moreover, transthoracic echocardiography gives the additional information that influences the operative technique of choice and identifies the high-risk patients (cardiac tamponade, severe aortic dilatation, severe aortic regurgitation). Our retrospective analysis confirms the pivotal role of TTE in the evaluation of the patients with suspected proximal aortic dissection in emergency room setting.

Factor XIII expression within aortic valves and its plasma activity in patients with aortic stenosis: association with severity of disease

Aortic valve stenosis (AS) shares several similarities with atherosclerosis. Factor XIII (FXIII) has been detected within atherosclerotic plaques and may contribute to the development of atherosclerosis via multiple mechanisms. In the current study, we sought to investigate FXIII expression within human stenotic aortic valves and its association with severity of the disease. We prospectively enrolled 91 consecutive patients with AS scheduled for isolated valve replacement. Valvular FXIII subunit A (FXIII-A), fibrin and macrophages expression was evaluated by immunostaining. FXIII-A subunit transcripts and FXIII-A Val34Leu polymorphism was determined by real-time PCR. Plasma FXIII (pFXIII) activity was measured. We demonstrated that the valvular FXIII-A was predominantly expressed on the aortic side of leaflets, colocalized with alternatively activated macrophages (AAM). Areas stained for FXIII-A showed positive correlations with valvular fibrin presence, degree of calcification, pFXIII activity and the severity of AS, reflected by mean and maximum transvalvular gradients (all, p<0.001). The FXIII-A mRNA in the stenotic leaflets was significantly elevated compared to control leaflets. Interestingly, pFXIII activity was also positively correlated with mean (p<0.001) and maximum (p=0.001) transvalvular gradient. The FXIII-A Val34Leu polymorphism did not affect FXIII-A and fibrin expression in AS valves. In conclusion, the study is the first to show abundant expression of FXIII-A at the mRNA and protein levels within human stenotic aortic valves, which is associated with the severity of AS. Our findings might suggest that FXIII in the stenotic valves is presented in AAM and may be involved in the AS progression.

New diastolic cardiomyopathy in patients with severe accidental hypothermia after ECMO rewarming: a case-series observational study

IntroductionAccidental hypothermia is a condition associated with significant morbidity and mortality. Hypothermia has been reported to affect left ventricular systolic and diastolic function. However, most of the data come from animal experimental studies.Aim of the studyThe purpose of the present study was to assess the impact of severe accidental hypothermia on systolic and diastolic ventricular function in patients treated using veno-arterial extracorporeal membrane oxygenation (ECMO).MethodsWe prospectively assessed nine hypothermic patients (8 male, age 25–78 years) who were transferred to the Severe Accidental Hypothermia Center and treated with ECMO. Transthoracic echocardiography was performed on admission (in patients without cardiac arrest) and on discharge from ICU after achieving cardiovascular stability. Cardiorespiratory stability and full neurologic recovery was achieved in all patients.ResultsBiomarkers of myocardial damage (CK, CKMB, hsTnT) were significantly elevated in all study patients. Admission echocardiography performed in patients in sinus rhythm, revealed moderate-severe bi-ventricular systolic dysfunction and moderate bi-ventricular diastolic dysfunction. Discharge echocardiography showed persistent mild bi-ventricular diastolic dysfunction, although systolic function of both ventricles returned to normal. Discharge echocardiography in patients admitted with cardiac arrest showed normal (5 patients) or moderately impaired (1 patient) global LV systolic function on discharge. However, mild or moderate LV diastolic dysfunction was observed in all 6 patients. Discharge RV systolic function was normal, whereas mild RV diastolic dysfunction was present in these patients.ConclusionAfter severe accidental hypothermia bi-ventricular diastolic dysfunction persists despite systolic function recovery in survivors treated with ECMO.

Ultrasonographic caval indices do not significantly contribute to predicting fluid responsiveness immediately after coronary artery bypass grafting when compared to passive leg raising

BackgroundAppropriate fluid management is one of the most important elements of early goal-directed therapy after cardiothoracic surgery. Reliable determination of fluid responsivenss remains the fundamental issue in volume therapy.The purpose of the study was to assess the usefulness of dynamic IVC-derived parameters (collapsibility index, distensibility index) in comparison to passive leg raising, in postoperative fluid management in mechanically ventilated patients with left ventricular ejection fraction ≥ 30 %, immediately after elective coronary artery bypass grafting.MethodsProspective observational case series study including 35 patients with LVEF ≥ 30 %, undergoingelective coronary artery bypass grafting was conducted. Transthoracic echocardiography, passive leg raising and intravenous administration of saline were performed in all study subjects. Dynamic parameters derived from ultrasonographic assessment of the IVC diameter (collapsibility index–CI and distensibility index–DI), cardiac outputResultsThere were 24 (68.57 %) responders in the study population. There were no statistical differences between the groups in relation to: clinical parameters, pre- and postoperative LVEF, fluid balance and CVP. Change in cardiac output after passive leg raising correlated significantly with that after the volume expansion (p=0.000, r=0.822). Dynamic IVC derivatives were slightly higher in fluid responders, however this trend did not reach statistical significance. None of the caval indices correlated with fluid responsiveness.ConclusionDynamic IVC-derived parameters do not predict fluid responsiveness in mechanically ventilated patients with preserved ejection fraction immediately after elective coronary artery bypass grafting. Passive leg raising is not inferior to volume expansion in differentiating between fluid responders and nonresponders. Immediate fluid challenge after CABG is safe and well tolerated.

Prothrombotic State in Patients With a Left Atrial Appendage Thrombus of Unknown Origin and Cerebrovascular Events

Background and Purpose— We hypothesized that formation of left atrial appendage (LAA) thrombi of unknown origin is associated with altered fibrin clot properties and blood hypercoagulability. Methods— In a case–control study, we investigated 32 patients with a history of LAA thrombus after successful anticoagulant treatment versus 32 control subjects matched for age, sex, and diabetes mellitus. All subjects had previous ischemic stroke, transient ischemic attack, or migraine associated with patent foramen ovale. Patients with documented atrial fibrillation were excluded. We determined plasma fibrin clot permeability, fibrinolytic efficiency, thrombin generation, platelet and endothelial markers. Stroke or transient ischemic attack were assessed during a median follow-up of 74 (range 19–98) months. Results— Compared with controls, patients with LAA thrombus more frequently were smokers (43.8% versus 18.8%) and had 20% prolonged clot lysis time, lower plasminogen (−14%), and higher plasminogen activator inhibitor-1 (+17%), thrombin–antithrombin complexes (+17%), CD40 ligand (+30%), P-selectin (+29%), and von Willebrand factor (+30%, all P<0.05). Occurrence of LAA thrombus was predicted by von Willebrand factor (&bgr;=0.038, P=0.004), plasminogen (&bgr;=−0.048, P=0.01), plasminogen activator inhibitor-1 (&bgr;=−0.161, P=0.03), and clot permeability (&bgr;=−1.076, P=0.03). During follow-up, cerebrovascular events occurred in 10 (33.33%) of the 30 available patients in the LAA thrombus group, including 7 (23.3%) with recurrent LAA thrombus and 4 (13.33%) with documented atrial fibrillation. Recurrent LAA thrombus was associated with lower baseline Ks and higher thrombin generation, fibrinogen, plasminogen activator inhibitor-1, and soluble CD40 ligand (all P<0.05). Conclusions— Prothrombotic blood alterations could be involved in the LAA thrombus formation in patients without documented atrial fibrillation and are associated with increased risk of stroke or transient ischemic attack during follow-up.

Effectiveness and Validity of Sonographic Upper Airway Evaluation to Predict Difficult Laryngoscopy

Our objective was to evaluate the effectiveness of 9 airway sonographic parameters imaged from the submandibular view as predictors of difficult laryngoscopy. Additionally, we aimed to evaluate the validity of the models of combined sonographic and clinical tests in predicting difficult laryngoscopy.