Factor Xa inhibition and sPESI failure in intermediate-high-risk pulmonary embolism.

We report the case of a 61-year-old man who presented at the Emergency Department (ED), complaining of sudden-onset dyspnea and chest pain after a long flight from Tokyo to Houston. Considering his clinical stability and sPESI 0, enoxaparin 1 mg/kg BID was started for 24 h, and the patient was then considered for early discharge with apixaban 10 mg BID. Direct-factor Xa inhibition did not improve extensive thrombus burden and right ventricular dysfunction despite D-dimer measurement reduction. Because of the treatment failure, we considered thrombolysis. Currently, recommendations to use thrombolysis in patients under non-vitamin K antagonist oral anticoagulants (NOACs) do not exist. Hence, the one dose of apixaban was stopped, and 12 h later, we performed successful thrombolysis. A systematic review from 2007 to 2017 did not identify any cases related to NOACs failure to reduce thrombus burdens in patients with PE and persistent right ventricular dysfunction. We also did not find any evidence of cases that reported strategies for urgent thrombolysis in PE patients on NOACs. To the best of our knowledge, apixaban's failure to reduce thrombus burden, persistent right ventricular dysfunction, and a NOACs-thrombolysis bridge in patients with PE on apixaban has not been previously described. Both the bedside risk stratification and the therapeutic failures should alert clinicians in the ED to the potential limitations of low-molecular-weight heparin, NOACs therapy, and sPESI in the setting of intermediate-high-risk PE.

High proportion of patients with end-stage heart failure regardless of aetiology demonstrates anti-cardiac antibody deposition in failing myocardium: humoral activation, a potential contributor of disease progression.

AIMS: Various reports have raised the possibility of humoral immune responses as contributors for the progression of heart failure. Previous studies, however, have focused on the analysis of serum and documented circulating antibodies against a variety of cardiac proteins. However, there is little evidence on whether anti-cardiac antibodies are deposited in end-stage failing myocardium. Our objective was to determine whether or not there was evidence of deposition of anti-cardiac antibodies and/or activated complement components in end-stage failing human myocardium. METHODS AND RESULTS: Myocardial samples were obtained from 100 end-stage heart failure patients and 40 donor control biopsies. Sections were cut and stained using standard fluorescent immunohistochemistry techniques with anti-human immunoglobulin G (IgG), IgG3, and C3c. Gel electrophoresis and protein identification by mass spectrometry were used to confirm the presence of IgG and its antigen. Immunoglobulin G was localized to the sarcolemma in 71% of patients, 48% of those being positive for the subtype IgG3. The proportion of patients with ischaemic heart disease that was positive for IgG was 65% and among those with non-ischaemic aetiologies was 76%. In a subgroup analysis, the presence of IgG and its subunits were confirmed by mass spectrometry and adenosine triphosphate synthase ß subunit identified as an antigen. Complement was activated in 31% of all patients. The presence of IgG, IgG3, and C3c was directly correlated with the length of disease (r = 0.451, P = 0.006). CONCLUSION: Evidence of anti-cardiac antibodies and complement activation was found in a large number of patients with end-stage cardiomyopathy regardless of the aetiology. Adenosine triphosphate synthase appears to be a new prominent antigenic stimulus; but more interestingly, the simultaneous co-existence of activated complement components suggests that this humoral mechanism may participate in disease progression.

Evaluation of left ventricular function using volumetric computed tomography in the clinical setting.

OBJECTIVE: To correlate the left ventricular parameters obtained with 64-slice Volumetric Computed Tomography (VCT) with those obtained with the reference standard, cardiovascular magnetic resonance (CMR) imaging. METHODS: VCT and a 3.0T MRI scanner were used. Results from both studies were independently evaluated by two cardiologists. A linear correlation and a paired Student's t test were used to analyze the data with a P<0.05 being considered significant. RESULTS: Thirty consecutive patients were evaluated with VCT and CMR. The left ventricular indices for CMR and VCT were, respectively, mass 86.4±25.8 vs. 82.7±27.6g (P=0.31); ESV 45.5±27.8 vs. 48.7±40.4ml (P=.405); EDV 101.3±32.7 vs. 105.1±44.0ml (P=0.475); SV 55.9±16.1 vs. 56.8±15.6ml (P=0.713); LVEF 57.5±13.2% vs. 56.9±12.4% (P=0.630). No differences in intraobserver variability for both methods were found, CT r=0.96, r(2)=0.92 P<0.0001 and MR r=0.96 r(2)=0.93 P<0.0001. There was no significant statistical difference in the presence of artifacts. CONCLUSION: There is a close correlation between CMRI and VCT in the evaluation of LV function. VCT is as useful as 3T CMR, and could be incorporated as another resource for evaluating LV function.

Full Expression of Cardiomyopathy Is Partly Dependent on B-Cells: A Pathway That Involves Cytokine Activation, Immunoglobulin Deposition, and Activation of Apoptosis.

BACKGROUND: Limited information exists on the role of B-cell-dependent mechanisms in the progression of heart failure (HF). However, in failing human myocardium, there is evidence of deposition of activated complement components as well as anticardiac antibodies. We aimed to determine the contribution of B-cells in HF progression using a nonsurgical mouse model of nonischemic cardiomyopathy (CMP). METHODS AND RESULTS: CMP protocol involved the use of l-NAME and NaCl in the drinking water and angiotensin-II infusion for 35 days. At day 35, mice were analyzed by cardiac magnetic resonance imaging, gene expression, and histology. Mice (12 weeks old) were divided into 4 groups, all in C57BL/6 background: wild-type (WT) CMP; severe combined immunodeficiency (SCID) CMP (T- and B-cell deficient); CD22(-) CMP (B-cell depleted); and Nude CMP (T-cell deficient), with their respective controls. We performed B-cell depletion and reconstitution protocols. The protective effect of B-cell depletion was demonstrated by a significant reduction of cell hypertrophy and collagen deposition and a preserved ejection fraction in the CD22(-) CMP group compared to WT CMP. Once SCID mice underwent B-cell reconstitution with isolated CMP B-cells, the CMP phenotype was restored. Furthermore, deposition of IgG3 and apoptosis in the myocardium follows the development of CMP; in addition, in vitro studies demonstrated that activated B-cells stimulate collagen production by cardiac fibroblasts. CONCLUSIONS: The absence of B-cells in this model of HF resulted in less hypertrophy and collagen deposition, preservation of left ventricular function, and, in association with these changes, a reduction in expression of proinflammatory cytokines, immunoglobulin G deposition, and apoptosis in the myocardium. Taken together, these data suggest that B-cells play a contributory role in an angiotensin-II-induced HF model.

The role of a multimodality imaging approach in diagnosis and stratification of aborted sudden cardiac death.

A 34-year-old man was admitted after an episode of aborted sudden cardiac death. The initial investigation including electrocardiogram, chest x-ray, transthoracic echocardiogram, and biomarkers were normal. Although coronary angiography showed nonsevere stenosis, optical coherence tomography revealed severe obstruction in the artery with a layered appearance of the vessel wall; it was consistent with the presence of mural thrombus.

The Brockenbrough-Braunwald-Morrow sign.

Hypertrophic cardiomyopathy is a relatively common genetic disorder and usually asymptomatic. However, approximately 25% of patients develop left ventricular outflow obstruction and can develop angina, syncope, or congestive heart failure. Initiation and titration of beta-blockade usually results in symptomatic improvement. Patients with medically refractory symptoms can see further symptomatic improvement and relief of obstruction with either surgical myectomy or alcohol septal ablation (ASA). Although surgical myectomy has been the gold standard, ASA has been shown in nonrandomized studies and a meta-analysis to be comparable. In patients undergoing ASA without a rest obstruction, the Brokenbrough-Braunwald-Morrow sign can be used to accurately determine the degree of left ventricular outflow tract (LVOT) obstruction prior to, during, and after ASA.

Does quantifying epicardial and intrathoracic fat with noncontrast computed tomography improve risk stratification beyond calcium scoring alone?

BACKGROUND: Noncontrast cardiac computed tomography allows calculation of coronary artery calcium score (CACS) and measurement of epicardial adipose tissue (EATv) and intrathoracic fat (ITFv) volumes. It is unclear whether fat volume information contributes to risk stratification. METHODS AND RESULTS: Cardiac computed tomography was performed in 760 consecutive patients with acute chest pain admitted thorough the emergency department. None had prior coronary artery disease. CACS was calculated using the Agatston method. EATv and ITFv were semiautomatically calculated. Median patient follow-up was 3.3 years. Mean patient age was 54.4±13.7 years and Framingham risk score 8.2±8.2. The 45 patients (5.9%) with major acute cardiac events (MACE) were older (64.8±13.9 versus 53.7±13.4 years), more frequently male (60% versus 40%), and had a higher median Framingham risk score (16 versus 4) and CACS (268 versus 0) versus those without events (all P<0.01). The MACE group had a higher median of EATv (154 versus 116 mL) and ITFv (330 versus 223 mL), and a higher prevalence of EATv >125 mL (67% versus 44%) and ITFv >250 mL (64% versus 42%) (all P<0.01). CACS, EATv, and ITFv were all independently associated with MACE. CACS was associated with MACE after adjustment for fat volumes (P<0.0001), whereas EATv and ITFv improved the risk model only in patients with CACS >400. CONCLUSIONS: CACS and fat volumes are independently associated with MACE in acute chest pain patients and beyond that provided by clinical information alone. Although fat volumes may add prognostic value in patients with CACS >400, CACS is most strongly correlated with outcome.

Increased right-to-left ventricle diameter ratio is a strong predictor of right ventricular failure after left ventricular assist device.

BACKGROUND: Predictors of right ventricular failure (RVF) in patients with left ventricular assist devices (LVADs) have not been fully elucidated and are comprised mostly of clinical variables. We evaluated echocardiographic parameters associated with adverse outcomes in this population. METHODS: Transthoracic echocardiograms (TTEs) before continuous-flow LVAD implantation were analyzed in 109 patients. Twenty-six 2-dimensional and Doppler parameters were assessed for their association with the primary outcome of 30-day RVF, defined as a requirement of an RV assist device or ≥ 14 consecutive days of inotropic support, and the secondary composite outcome of 30-day death or RVF. Multivariate analysis adjusted for known clinical risk prediction models was performed. RESULTS: Overall, 25 (22.9%) and 27 (24.8%) patients reached the primary and secondary end-points, respectively. An increased RV/LV diameter ratio was the only TTE variable independently associated with both the primary (odds ratio [OR] = 5.40; 95% confidence interval [CI] 2.40 to 12.40; p = 0.012) and secondary (OR = 2.70; 95% CI 1.06 to 6.22; p = 0.03) outcomes after multivariate analysis. Scatterplot analysis with regression determined the optimal cut-off value for RV/LV diameter to be 0.75. Based on receiver operating characteristic curves, an increased RV/LV diameter ratio provided an additional predictive value to clinical risk scores. CONCLUSIONS: A TTE-measured RV/LV diameter ratio of ≥0.75 is independently associated with a higher risk for RVF in patients with continuous-flow LVAD. When used alone, this simple, easily derived, practical echocardiographic measurement has a predictive value equivalent to known clinical risk scores, whereas their combination provides stronger risk prediction for adverse outcomes.