Introduction: In pulmonary embolism (PE) without hemodynamic compromise, the prognostic value of right ventricular (RV) dysfunction as measured by echocardiography, computed tomography (CT) or biological (natriuretic peptides) markers has only been assessed in small studies. Methods: Databases were searched using the combined medical subject headings for right ventricular dysfunction or right ventricular dilatation with the exploded term acute pulmonary embolism. This retrieved 8 echocardiographic marker based studies (n = 1249), three CT marker based studies (n = 503) and 7 natriuretic peptide based studies (n = 582). A meta-analysis of these data was performed with the primary endpoint of mortality within three months after pulmonary embolism, and a secondary endpoint of overall mortality and morbidity by pulmonary embolism. Results: Patients with PE without hemodynamic compromise on admission and the presence of RV dysfunction determined by echocardiography and biological markers were associated with increased short-term mortality (odds ratio (OR) _ECHO = 2.36; 95% confidence interval (CI): 1.3-43; OR _BNP = 7.7; 95% CI: 2.9-20) while CT was not (OR_CT = 1.54-95% CI: 0.7-3.4). However, corresponding pooled negative and positive likelihood ratios independent of death rates were unsatisfactory for clinical usefulness in risk stratification. Conclusions: The presence of echocardiographic RV dysfunction or elevated natriuretic peptides is associated with short-term mortality in patients with pulmonary embolism without hemodynamic compromise. In contrast, the prognostic value of RV dilation on CT has yet to be validated in this population. As indicated both by positive and negative likelihood ratios the current prognostic value in clinical practice remains very limited.

Background: Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient mortality. Little is known about the prototypes of CAV trajectories at the population level. We aimed to identify the different evolutionary profiles of CAV and to determine the respective contribution of immune and nonimmune factors in CAV development. Methods: Heart transplant recipients were from 4 academic centers (Pitié-Salpêtrière and Georges Pompidou Hospital, Paris, Katholieke Universiteit Leuven, and Cedars-Sinai, Los Angeles; 2004–2016). Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessments of clinical, histological, and immunologic parameters. The main outcome was a prediction for CAV trajectory. We identified CAV trajectories by using unsupervised latent class mixed models. We then identified the independent predictive variables of the CAV trajectories and their association with mortality. Results: A total of 1301 patients were included (815 and 486 in the European and US cohorts, respectively). The median follow-up after transplantation was 6.6 (interquartile range, 4–9.1) years with 4710 coronary angiographies analyzed. We identified 4 distinct profiles of CAV trajectories over 10 years. The 4 trajectories were characterized by (1) patients without CAV at 1 year and nonprogression over time (56.3%), (2) patients without CAV at 1 year and late-onset slow CAV progression (7.6%), (3) patients with mild CAV at 1 year and mild progression over time (23.1%), and (4) patients with mild CAV at 1 year and accelerated progression (13.0%). This model showed good discrimination (0.92). Among candidate predictors assessed, 6 early independent predictors of these trajectories were identified: donor age ( P <0.001), donor male sex ( P <0.001), donor tobacco consumption ( P =0.001), recipient dyslipidemia ( P =0.009), class II anti–human leukocyte antigen donor-specific antibodies ( P =0.004), and acute cellular rejection ≥2R ( P =0.028). The 4 CAV trajectories manifested consistently in the US independent cohort with similar discrimination (0.97) and in different clinical scenarios, and showed gradients for overall-cause mortality ( P <0.001). Conclusions: In a large multicenter and highly phenotyped prospective cohort of heart transplant recipients, we identified 4 CAV trajectories and their respective independent predictive variables. Our results provide the basis for a trajectory-based assessment of patients undergoing heart transplantation for early risk stratification, patient monitoring, and clinical trials. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04117152.

Introduction: The relationship between brain natriuretic peptide (BNP) increase in acute pulmonary embolism (PE) and the increase in mortality and morbidity has frequently been suggested in small studies but its global prognostic performance remains largely undefined. We performed a systematic review and meta-analysis of data to examine the prognostic value of elevated BNP for short-term all-cause mortality and serious adverse events. Methods: The authors reviewed PubMed, BioMed Central, and the Cochrane database and conducted a manual review of article bibliographies. Using a prespecified search strategy, we included a study if it used BNP or N-terminal pro-BNP biomarkers as a diagnostic test in patients with documented PE and if it reported death, the primary endpoint of the meta-analysis, in relation to BNP testing. Studies were excluded if they were performed in patients without certitude of PE or in a subset of patients with cardiogenic shock. Twelve relevant studies involving a total of 868 patients with acute PE at baseline were included in the meta-analysis using a random-effects model. Results: Elevated BNP levels were significantly associated with short-term all-cause mortality (odds ratio [OR] 6.57, 95% confidence interval [CI] 3.11 to 13.91), with death resulting from PE (OR 6.10, 95% CI 2.58 to 14.25), and with serious adverse events (OR 7.47, 95% CI 4.20 to 13.15). The corresponding positive and negative predictive values for death were 14% (95% CI 11% to 18%) and 99% (95% CI 97% to 100%), respectively. Conclusion: This meta-analysis indicates that, while elevated BNP levels can help to identify patients with acute PE at high risk of death and adverse outcome events, the high negative predictive value of normal BNP levels is certainly more useful for clinicians to select patients with a likely uneventful follow-up.

Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single‐center, single‐arm, open‐label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre‐formed donor‐specific antibodies (DSA) were eligible. In addition to standard of care, patients received 9 infusions of eculizumab during the first two months post‐transplant. The primary composite endpoint was antibody‐mediated rejection (AMR) ≥ pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90‐97%) and 6,250 (5,000‐10,000), respectively. Retrospective B‐cell and T‐cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in 4 patients (20%). Survival at 1‐year was 90% with no deaths resulting from AMR. In a pre‐specified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy‐proven AMR in patients treated with eculizumab (HR=0.36, 95%CI=0.14‐0.95, p=0.032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk.

We sought to describe our experience with major coronary anomalies (MCAs) diagnosed in transthoracic echocardiography (TTE) in a large adult and paediatric population. MCAs may have serious clinical consequences. No echocardiographic studies have prospectively screened MCA in a general adult and paediatric population. From June 2008 to January 2012, a systematic search for MCA was prospectively conducted in children and adult patients, coming for a TTE. Three thousand five hundred and two patients (84% adults and 16% children) underwent a TTE. Fourteen coronary anomalies (0.39%) were diagnosed: nine anomalous origins of coronary artery from the opposite sinus with inter-arterial course, one abnormal left coronary artery from the pulmonary artery, three single coronary ostia, and one coronary fistula. Cardiac symptoms initiated investigation in seven patients. Five patients underwent specific surgery: two coronary reimplantations and three coronary bypass grafting. Ten patients had already undergone at least one TTE with the anomalous coronary artery being neither diagnosed nor suspected. MCA is a rare condition. TTE appears to be a potentially useful modality for the initial screening of MCA in adults and children, provided special attention is paid to coronary artery analysis.