Diuretics versus volume expansion in acute submassive pulmonary embolism.

BACKGROUND: The benefit of volume expansion (VE) in submassive pulmonary embolism (PE) with right ventricular (RV) dysfunction is unclear. AIM: To compare the effects of diuretic treatment versus VE in patients hospitalized for PE with RV dysfunction. METHODS: We prospectively included 46 consecutive patients with submassive PE treated on admission with a 40mg bolus of furosemide (D group, n=24) or 500mL of saline infusion (VE group, n=22). The primary endpoint was the timing of normalization of B-type natriuretic peptide and troponin Ic concentrations. The secondary endpoints were variations in RV function variables, recorded at baseline, at the 4th hour after treatment initiation (H4) and every day until discharge, and a clinical composite endpoint of thrombolysis or death at 7 and 30 days. RESULTS: No differences were observed between patients at baseline. The primary endpoint occurred earlier in the D group than in the VE group (67.5±34.8 vs 111.6±63.3hours; P=0.006). Furosemide treatment on admission was well tolerated, and was not associated with serious adverse events. At H4, substantial improvements were observed in the D group versus the VE group in terms of heart rate reduction (-8.15±21.0 vs -0.71±6.30 beats/min; P<0.01) and peak tricuspid annular systolic velocity (Doppler tissue imaging) (11.4±2.10 vs 9.90±2.80cm/s; P=0.02). There was no significant difference between groups in terms of severe outcomes at 7 and 30 days. CONCLUSIONS: In the acute management of submassive PE patients, a single furosemide bolus on admission seems to produce significant and earlier improvements in RV function markers compared with VE, without adverse events.

Cardiac remodelling amongst adults with various aetiologies of pulmonary arterial hypertension including Eisenmenger syndrome-implications on survival and the role of right ventricular transverse strain.

AIMS: Survival in pulmonary arterial hypertension (PAH) and Eisenmenger syndrome (ES) relates to right ventricular (RV) function. Little is known about differences of ventricular function between ES patients and those suffering from other PAH aetiologies. In this study, we compared global ventricular function assessed by speckle-tracking in adult patients with ES, other PAH aetiologies, or healthy controls; and assessed the relationship between ventricular function and survival. METHODS AND RESULTS: We performed a prospective cohort study recruiting 83 adult PAH patients (43 ES and 40 other PAH aetiologies patients) and 37 controls between March 2011 and June 2015. Patients with complex congenital heart disease were excluded. Fifty-three patients (63.9%) were in NYHA functional class ≥III at baseline and 60 (72.3%) were on advanced therapies. Mean RV peak longitudinal strain was -16.3 ± 7% in ES, lower compared with healthy controls (P < 0.001) but similar to other PAH aetiologies (P = 0.6). Mean RV peak transverse strain was +26.1 ± 17% in ES, lower than in controls (P < 0.001) but higher than in other PAH aetiologies (P < 0.001). No difference was observed between ES and other PAH in LV circumferential and longitudinal strain. Over a median follow-up of 22.6 months (3.3-32.2), 22 (26.5%) patients died all from cardio-pulmonary causes. ES and RV peak transverse strain were independent predictors of survival. RV peak transverse strain ≤22% identified patients with a 14-fold increased risk of death. CONCLUSION: Right ventricular remodelling differs between adults with ES and other PAH aetiologies. ES and increased RV free wall transverse strain are associated with better survival.

Early detection of cardiac involvement in sarcoidosis with 2-dimensional speckle-tracking echocardiography.

BACKGROUND/OBJECTIVES: Cardiac sarcoidosis (CS) is associated with high morbidity and sudden death. The absence of specific symptoms and lack of diagnostic gold standard technique is challenging. New imaging methods could improve the diagnosis of CS. The aim of our study was to assess the role of left ventricular (LV) longitudinal and circumferential strain as estimated by 2D speckle-tracking imaging in patients with diagnosed sarcoidosis without cardiac involvement according to the current guidelines. We investigated the prevalence of LV strain impairment in this population and assessed its relationship with clinical outcomes, composite of mortality, heart failure, arrhythmia and/or secondarily development of CS and cardiac device implantation. METHODS AND RESULTS: We performed a prospective case-control longitudinal study including 35 patients with diagnosed sarcoidosis and normal cardiac function as assessed by standard transthoracic echocardiography and 35 healthy age- and gender-matched controls. All patients underwent a comprehensive echocardiographic study. Mean age of patients was 47.9±14.8years old (22 women). Compared with controls, global LV longitudinal strain (LV GLS) was reduced in sarcoidosis patients: (-17.2±3.1 vs -21.3±1.5%, p<0.0001). Circumferential LV strain was preserved in patients compared to controls (-19.9±-4.3% vs -21.3±1.5%, p=0.12). Impaired LV GLS was significantly associated with clinical outcomes (HR 1.56; [1.16-2.11], p<0.01) on univariate analysis. CONCLUSION: Speckle-tracking echocardiography revealed decreased longitudinal LV strain in sarcoidosis patients that was associated with outcomes. LV GLS may represent an early marker of myocardial involvement in sarcoidosis patients that needs to be studied further.

Speckle-tracking imaging in patients with Eisenmenger syndrome.

BACKGROUND: Adults with Eisenmenger syndrome have a survival advantage over those with idiopathic pulmonary arterial hypertension. Improved survival may result from preservation of right ventricular (RV) function. AIMS: To assess left ventricular (LV) and RV remodelling in patients with Eisenmenger syndrome compared to a control population, using speckle-tracking imaging. METHODS: Adults with Eisenmenger syndrome and healthy controls were enrolled into this prospective two-centre study. Patients with Eisenmenger syndrome with low acoustic windows, irregular heart rhythm or complex congenital heart disease were excluded. Clinical assessment, B-type natriuretic peptide (BNP), 6-minute walk test and echocardiography (including dedicated views to perform offline two-dimensional-speckle-tracking analysis) were performed on inclusion. RESULTS: Our patient population (n=37; mean age 42.3 ± 17 years) was mostly composed of patients with ventricular septal defect (37.8%) or atrial septal defect (35.1%). Compared with the control population (n=30), patients with Eisenmenger syndrome had reduced global LV longitudinal strain (-17.4 ± 3.5 vs. -22.4 ± 2.3; P<0.001), RV free-wall longitudinal strain (-15.0 ± 4.7 vs. -29.9 ± 6.8; P<0.001) and RV transverse strain (25.8 ± 25.0 vs. 44.5 ± 15.1; P<0.001). Patients with Eisenmenger syndrome also more frequently presented a predominant apical longitudinal and transverse strain profile. Among patients with Eisenmenger syndrome, those with a post-tricuspid shunt presented with reduced global LV longitudinal strain but increased RV transverse strain, compared to patients with pre-tricuspid shunt. CONCLUSION: Patients with Eisenmenger syndrome had impaired longitudinal RV and LV strain, but present a relatively important apical deformation. RV and LV remodelling, as assessed by speckle-tracking imaging, differ between patients with pre- and post-tricuspid shunt.

B blood group: A strong risk factor for venous thromboembolism recurrence.

BACKGROUND: Non-O blood group patients are at higher risk of first episode of venous thromboembolism (VTE). However, only little is known about the risk of recurrence according to the blood group. In this study, we aimed to determine the impact of ABO blood group on VTE recurrence. METHODS: We prospectively recruited 106 consecutive patients with a first documented episode of pulmonary embolism (PE). Patients were followed at least 12months after anticoagulation discontinuation. The main endpoint was recurrence of symptomatic VTE. RESULTS: Data from 100 patients were analyzed. Median follow-up was 28months [24-34.8]. PE was unprovoked in 48 patients. Mean anticoagulation duration was 5.3±2.2months. The rate of VTE recurrence was 12.7 per 100 patient-years (30 recurrences). B blood group patients had a 2.7-fold increased risk of VTE recurrence (95%CI 1.1-6.2, p=0.03). On multivariate analysis, B blood group was the strongest independent predictor of VTE recurrence (Hazard Ratio (HR) 2.6, 95%CI 1.1-6.1, p=0.04). In contrast, A and AB blood groups were not associated with VTE recurrence. VTE recurrences were less frequent in O blood group compared to non-O patients (HR 0.5, 95%CI 0.2-1.1, p=0.09). O blood group women had a 5-fold decreased risk of VTE recurrence (HR 0.2, 95%CI 0.1-0.8, p=0.01). CONCLUSIONS: Non-O blood groups, beyond being involved in the occurrence of a first VTE event, also contribute to VTE recurrence. B blood group is strongly associated with VTE recurrence, thus high-risk B blood group patients could benefit from long-term anticoagulation therapy after a first VTE event.

Patent foramen ovale and stroke in intermediate-risk pulmonary embolism.

BACKGROUND: Patent foramen ovale (PFO) in pulmonary embolism (PE) is associated with an increased risk of complications. However, little is known about PFO and ischemic stroke prevalence, particularly in acute intermediate-risk PE. In addition, in this context, the so-called "gold standard" method of PFO diagnosis remains unknown. We aimed to evaluate PFO and ischemic stroke prevalence and determine which of transesophageal echocardiography (TEE) or transthoracic echocardiography (TTE) is the best PFO diagnostic method in this context. METHODS: We conducted a prospective monocentric study of consecutive patients with intermediate-risk PE in whom a TEE and TTE with contrast were performed. Brain MRI was used to confirm clinically obvious strokes or to diagnose subclinical ones. RESULTS: Forty-one patients with intermediate-risk PE were identified over a 9-month period. Contrast TEE revealed PFO in 56.1%, whereas contrast TTE showed PFO in only 19.5% (P < .001). Of note, all PFOs observed with TTE were also diagnosed by TEE. Ischemic stroke occurred in 17.1% and was always associated with PFO and large shunt. CONCLUSIONS: PFO and related ischemic strokes are frequent in intermediate-risk PE. TEE is much more efficient than TTE for PFO diagnosis. Considering the high risk of intracranial bleeding with thrombolysis in PE, which may be partly due to hemorrhagic transformation of subclinical strokes, screening PFO with TEE should be considered in intermediate-risk PE when thrombolytic treatment is discussed.

Imaging in pulmonary hypertension: Focus on the role of echocardiography.

Patients with pulmonary hypertension must be evaluated using a multimodality approach to ensure a correct diagnosis and basal evaluation as well as a prognostic assessment. Beyond the assessment of pulmonary pressures, the echocardiographical examination allows the evaluation of right ventricular adaptation to elevated afterload. Numbers of variables are commonly used in the assessment of the pulmonary hypertension patient in order to detect changes in right heart geometry, right-to-left interaction and right ventricular dysfunction. Whereas an isolated change in one echocardiographical variable is not meaningful, multiple echocardiographical variable modifications together provide accurate information. In this review, we will link pulmonary hypertension pathophysiological changes with echocardiographical indices and describe the clinical implications of echocardiographical findings.

Real time three-dimensional echocardiographic assessment of left ventricular function in heart failure patients: underestimation of left ventricular volume increases with the degree of dilatation.

BACKGROUND: Accurate quantification of left ventricular (LV) volumes and ejection fraction (EF) is of critical importance. Cardiac magnetic resonance (CMR) is considered as the reference and three-dimensional echocardiography (3DE) is an accurate method, but only few data are available in heart failure patients. We therefore sought to compare the accuracy of real time three-dimensional echocardiography (RT3DE) and two-dimensional echocardiography (2DE) for quantification of LV volumes and EF, relative to CMR imaging in an unselected population of heart failure patients. METHODS AND RESULTS: We studied 24 patients (17 men, age 58 ± 15 years) with history of heart failure who underwent echocardiographic assessment of LV function (2DE, RT3DE) and CMR within a period of 24 hours. Mean LV end-diastolic volume (LVEDV) was 208 ± 109 mL (121 ± 64 mL/m(2) ) and mean LVEF was 31 ± 12.8%. 3DE data sets correlate well with CMR, particularly with respect to the EF (r: 0.8, 0.86, and 0.95; P < 0.0001 for LVEDV, LVESV, and EF, respectively) with small biases (-55 mL, -44 mL, 1.1%) and acceptable limits of agreement. RT3DE provides more accurate measurements of LVEF than 2DE (z= 2.1, P = 0.037) and lower variability. However, 3DE-derived LV volumes are significantly underestimated in patients with severe LV dilatation. In patients with LVEDV below 120 mL/m(2) , RT3DE is more accurate for volumes and EF evaluation. CONCLUSION: Compared with CMR, RT3DE is accurate for evaluation of EF and feasible in all our heart failure patients, at the expense of a significant underestimation of LV volumes, particularly when LVEDV is above 120 mL/m(2) .

Timing of troponin I measurement in pulmonary embolism.

BACKGROUND: Troponin I (TnI) is an important prognostic marker and risk-stratification tool in patients with pulmonary embolism (PE). However, the best timing for this biomarker measurement is still unclear. OBJECTIVE: To analyse the kinetics of TnI in patients hospitalised for PE in order to better ascertain the evolution of the biomarker in this disease. In particular, we attempted to determine which measurement is the most appropriate to assess the PE risk according to this biomarker's status. DESIGN, SETTING, PATIENTS AND MAIN OUTCOME MEASURES: This was a prospective, single center, cohort study. TnI (Beckman Access method) was measured on admission, then every 8 h for 72 h in 200 stable patients hospitalised for PE in our cardiology department. Patients were classified into two groups: TnI-(negative) or TnI +. RESULTS: Mean TnI peak occurred at H8: 0.67±0.55 ng/ml. TnI values then decreased quickly, but remained positive (>0.06 ng/ml) beyond the 72-h surveillance period. The TnI biological profile varied widely after admission. Of the patients TnI- on the first assessment, 15% were positive at the second measurement. Among patients hospitalised less than 24 h after the onset of symptoms, 30% were misclassified on admission. In all cases, the second assessment, eight hours after admission, gave the biomarker's true status. CONCLUSION: Our study clarifies the kinetics of TnI in PE and highlights the situations in which an early TnI can be false negative. Many misclassifications could be avoided by taking into account the value of this biomarker obtained at H8.

Doubling the dose of clopidogrel restores the loss of antiplatelet effect induced by esomeprazole.

INTRODUCTION: Concerns have been raised about the potential adverse interaction between clopidogrel and PPIs. We studied the impact of esomeprazole and ranitidine on the antiplatelet action of clopidogrel and aspirin and sought to determine whether doubling the dose of clopidogrel could restore its efficacy. MATERIALS AND METHODS: In a randomized prospective crossover study, we tested platelet reactivity to aspirin and clopidogrel (75 and 150 mg) with and without esomeprazole or ranitidine using the VerifyNow system (Accumetrics Inc, San Diego, CA, USA) in 4 stages, each lasting 7 days: T1, 160 mg aspirin and 75 mg clopidogrel; T2 : 160 mg aspirin+75 mg clopidogrel+20 mg esomeprazole, T3 : 160 mg aspirin+150 mg clopidogrel+20 mg esomeprazole and T4 : 160 mg aspirin+75 mg clopidogrel+150 mg ranitidine. Results are expressed in P2Y12 Reaction Units (PRU%) and Aspirin Reaction Units (ARU). RESULTS: In 21 patients with stable coronary artery disease, esomeprazole reduced the effect of clopidogrel with a 38.6%±24 loss in PRU% (p<0.001) (absolute mean difference -16.7 PRU% [-21;-12.5]), increasing 8-fold the prevalence of low responders to clopidogrel (defined as patients with PRU% below 20%). Doubling clopidogrel dosage to 150 mg restored the basal response. Ranitidine did not modify the antiplatelet effect of clopidogrel. CONCLUSION: Our study demonstrates a strong negative clopidogrel/esomeprazole interaction, compensated by increasing the dose of clopidogrel to 150 mg or replacing esomeprazole with ranitidine. That could offer a simple solution to the PPI-induced clopidogrel resistance.

Coronary syndromes following aspirin withdrawal: a special risk for late stent thrombosis.

OBJECTIVES: We sought to determine whether aspirin withdrawal is an encountered situation in coronary disease patients who relapsed. BACKGROUND: Despite the recognized benefits of aspirin in coronary disease, and because of the threat of bleeding or poor compliance, aspirin intake is sometimes stopped. It is not known whether withdrawal of aspirin can be harmful in coronary-disease patients. METHODS: Between September 1999 and April 2002, a total of 1,236 patients hospitalized for acute coronary syndrome (ACS) were questioned in order to determine whether aspirin intake had been interrupted. RESULTS: Fifty-one of these ACSs occurred within 1 month after aspirin withdrawal. This represents 4.1% of all coronary events but 13.3% of recurrences. Among those patients who relapsed, the incidence of ST-segment elevation ACS was higher in those who stopped aspirin when compared to the 332 patients who did not stop aspirin (39% vs. 18%; p = 0.001). Ten (20%) cases involved a thrombosis of an uncoated stent implanted on average 15.5 +/- 6.5 months previously. Mean delay between aspirin withdrawal and the acute coronary event was 10 +/- 1.9 days. Reasons for aspirin withdrawal included minor surgery in 7 cases, fibroscopy in 8 cases, dental treatment in 13 cases, bleeding in 3 cases, and patient non-compliance in 20 cases. CONCLUSIONS: Our results support the hypothesis that aspirin withdrawal in coronary patients may represent a real risk for the occurrence of a new coronary event. Many cases involved late uncoated-stent thrombosis. Assessment of the exact incidence of coronary recurrences after aspirin withdrawal will need prospective studies.